Advertisement

Phenotype, Compartmental Organization and Differential Vulnerability of Nigral Dopaminergic Neurons

  • Tomás González-HernándezEmail author
  • Domingo Afonso-Oramas
  • Ignacio Cruz-Muros
Chapter
Part of the Journal of Neural Transmission. Supplementa book series (NEURALTRANS, volume 73)

Abstract

The degeneration of nigral dopaminergic (DA-) neurons is the histopathologic hallmark of Parkinson’s disease (PD), but not all nigral DA-cells show the same susceptibility to degeneration. This starts in DA-cells in the ventrolateral and caudal regions of the susbtantia nigra (SN) and progresses to DA-cells in the dorsomedial and rostral regions of the SN and the ventral tegmental area, where many neurons remain intact until the final stages of the disease. This fact indicates a relationship between the topographic distribution of midbrain DA-cells and their differential vulnerability, and the possibility that this differential vulnerability is associated with phenotypic differences between different subpopulations of nigral DA-cells. Studies carried out during the last two decades have contributed to establishing the existence of different compartments of nigral DA-cells according to their neurochemical profile, and a possible relationship between the expression of some factors and the relative vulnerability or resistance of DA-cell subpopulations to degeneration. These aspects are reviewed and discussed here.

Keywords

Mesolimbic Neurochemical profile Neurodegeneration Nigrostriatal Parkinson’s disease Substantia nigra 

Abbreviations

DA

Dopamine

DA-

Dopaminergic

PD

Parkinson’s disease

SN

Substantia nigra

SNC

Substantia nigra pars compacta

SNcv

Caudo-latero-ventral region of the substantia nigra

SNL

Substantia nigra pars lateralis

SNR

Substantia nigra pars reticulatata

SNrm

Rostro-medio-dorsal region of the substantia nigra

TH

Tyrosine hydroxylase

VTA

Ventral tegmental area

Notes

Acknowledgments

This work has been supported by the Ministerio de Educación y Ciencia de España (grant n° BFU2007/66561).

References

  1. Acampora D, Mazan S, Lallemand Y, Avantaggiato V, Maury M, Simeone A, Brulet P (1995) Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121:3279–3290PubMedGoogle Scholar
  2. Airaksinen MS, Thoenen H, Meyer M (1997) Vulnerability of midbrain dopaminergic neurons in calbindin-D28k-deficient mice: lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and weaver mice. Eur J Neurosci 9:120–127PubMedCrossRefGoogle Scholar
  3. Airaksinen MS, Titievsky A, Saarma M (1999) GDNF family neurotrophic factor signaling: four masters, one servant? Mol Cell Neurosci 13:313–325PubMedCrossRefGoogle Scholar
  4. Akerud P, Alberch J, Eketjall S, Wagner J, Arenas E (1999) Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons. J Neurochem 73:70–78PubMedCrossRefGoogle Scholar
  5. Altar CA, Boylan CB, Fritsche M, Jones BE, Jackson C, Wiegand SJ, Lindsay RM, Hyman C (1994) Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions. J Neurochem 63:1021–1032PubMedCrossRefGoogle Scholar
  6. Armentero MT, Fancellu R, Nappi G, Bramanti P, Blandini F (2006) Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson’s disease. Neurobiol Dis 22:1–9PubMedCrossRefGoogle Scholar
  7. Asano K, Chee CB, Gaston B, Lilly CM, Gerard C, Drazen JM, Stamler JS (1994) Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells. Proc Natl Acad Sci USA 91:10089–10093PubMedCrossRefGoogle Scholar
  8. Baimbridge KG, Celio MR, Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends Neurosci 15:303–308PubMedCrossRefGoogle Scholar
  9. Baloh RH, Tansey MG, Golden JP, Creedon DJ, Heuckeroth RO, Keck CL, Zimonjic DB, Popescu NC, Johnson EM Jr, Milbrandt J (1997) TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron 18:793–802PubMedCrossRefGoogle Scholar
  10. Barbacid M (1994) The Trk family of neurotrophin receptors. J Neurobiol 25:1386–1403PubMedCrossRefGoogle Scholar
  11. Barroso-Chinea P, Cruz-Muros I, Aymerich MS, Rodriguez-Diaz M, Afonso-Oramas D, Lanciego JL, Gonzalez-Hernandez T (2005) Striatal expression of GDNF and differential vulnerability of midbrain dopaminergic cells. Eur J Neurosci 21:1815–1827PubMedCrossRefGoogle Scholar
  12. Battaglia G, Busceti CL, Pontarelli F, Biagioni F, Fornai F, Paparelli A, Bruno V, Ruggieri S, Nicoletti F (2003) Protective role of group-II metabotropic glutamate receptors against nigro-striatal degeneration induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in mice. Neuropharmacology 45:155–166PubMedCrossRefGoogle Scholar
  13. Bean AJ, Elde R, Cao YH, Oellig C, Tamminga C, Goldstein M, Pettersson RF, Hokfelt T (1991) Expression of acidic and basic fibroblast growth factors in the substantia nigra of rat, monkey, and human. Proc Natl Acad Sci USA 88:10237–10241PubMedCrossRefGoogle Scholar
  14. Beckstead RM, Domesick VB, Nauta WJ (1979) Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res 175:191–217PubMedCrossRefGoogle Scholar
  15. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455PubMedCrossRefGoogle Scholar
  16. Berthele A, Laurie DJ, Platzer S, Zieglgansberger W, Tolle TR, Sommer B (1998) Differential expression of rat and human type I metabotropic glutamate receptor splice variant messenger RNAs. Neuroscience 85:733–749PubMedCrossRefGoogle Scholar
  17. Bettler B, Mulle C (1995) Review: neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacology 34:123–139PubMedCrossRefGoogle Scholar
  18. Bischoff S, Barhanin J, Bettler B, Mulle C, Heinemann S (1997) Spatial distribution of kainate receptor subunit mRNA in the mouse basal ganglia and ventral mesencephalon. J Comp Neurol 379:541–562PubMedCrossRefGoogle Scholar
  19. Bizon JL, Lauterborn JC, Gall CM (1999) Subpopulations of striatal interneurons can be distinguished on the basis of neurotrophic factor expression. J Comp Neurol 408:283–298PubMedCrossRefGoogle Scholar
  20. Bonsi P, Cuomo D, Picconi B, Sciamanna G, Tscherter A, Tolu M, Bernardi G, Calabresi P, Pisani A (2007) Striatal metabotropic glutamate receptors as a target for pharmacotherapy in Parkinson’s disease. Amino Acids 32:189–195PubMedCrossRefGoogle Scholar
  21. Bourque MJ, Trudeau LE (2000) GDNF enhances the synaptic efficacy of dopaminergic neurons in culture. Eur J Neurosci 12:3172–3180PubMedCrossRefGoogle Scholar
  22. Bozzi Y, Borrelli E (2006) Dopamine in neurotoxicity and neuroprotection: what do D2 receptors have to do with it? Trends Neurosci 29:167–174PubMedCrossRefGoogle Scholar
  23. Bradford HF, Zhou J, Pliego-Rivero B, Stern GM, Jauniaux E (1999) Neurotrophins in the pathogenesis and potential treatment of Parkinson’s disease. Adv Neurol 80:19–25PubMedGoogle Scholar
  24. Bredt DS, Snyder SH (1994) Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 63:175–195PubMedCrossRefGoogle Scholar
  25. Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH (1991) Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron 7:615–624PubMedCrossRefGoogle Scholar
  26. Breitwieser GE (2005) GIRK channels: hierarchy of control. Focus on "PKC-delta sensitizes Kir3.1/3.2 channels to changes in membrane phospholipid levels after M3 receptor activation in HEK-293 cells". Am J Physiol Cell Physiol 289:C509–C511PubMedCrossRefGoogle Scholar
  27. Brown AM, Birnbaumer L (1990) Ionic channels and their regulation by G protein subunits. Annu Rev Physiol 52:197–213PubMedCrossRefGoogle Scholar
  28. Burgoyne RD, Weiss JL (2001) The neuronal calcium sensor family of Ca2+-binding proteins. Biochem J 353:1–12PubMedCrossRefGoogle Scholar
  29. Burnashev N, Monyer H, Seeburg PH, Sakmann B (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8:189–198PubMedCrossRefGoogle Scholar
  30. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proc Natl Acad Sci USA 80:4546–4550PubMedCrossRefGoogle Scholar
  31. Campbell KJ, Takada M, Hattori T (1991) Co-localization of tyrosine hydroxylase and glutamate decarboxylase in a subpopulation of single nigrotectal projection neurons. Brain Res 558:239–244PubMedCrossRefGoogle Scholar
  32. Cass WA, Gerhardt GA (1994) Direct in vivo evidence that D2 dopamine receptors can modulate dopamine uptake. Neurosci Lett 176:259–263PubMedCrossRefGoogle Scholar
  33. Castillo SO, Baffi JS, Palkovits M, Goldstein DS, Kopin IJ, Witta J, Magnuson MA, Nikodem VM (1998) Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene. Mol Cell Neurosci 11:36–46PubMedCrossRefGoogle Scholar
  34. Cerruti C, Walther DM, Kuhar MJ, Uhl GR (1993) Dopamine transporter mRNA expression is intense in rat midbrain neurons and modest outside midbrain. Brain Res Mol Brain Res 18:181–186PubMedCrossRefGoogle Scholar
  35. Chadi G, Rosen L, Cintra A, Tinner B, Zoli M, Pettersson RF, Fuxe K (1993) Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat. Neuroreport 4:783–786PubMedCrossRefGoogle Scholar
  36. Charara A, Smith Y, Parent A (1996) Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates: Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistry. J Comp Neurol 364:254–266PubMedCrossRefGoogle Scholar
  37. Chittajallu R, Braithwaite SP, Clarke VR, Henley JM (1999) Kainate receptors: subunits, synaptic localization and function. Trends Pharmacol Sci 20:26–35PubMedCrossRefGoogle Scholar
  38. Chiueh CC, Burns RS, Markey SP, Jacobowitz DM, Kopin IJ (1985) Primate model of parkinsonism: selective lesion of nigrostriatal neurons by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine produces an extrapyramidal syndrome in rhesus monkeys. Life Sci 36:213–218PubMedCrossRefGoogle Scholar
  39. Cho J, Yarygina O, Oo TF, Kholodilov NG, Burke RE (2004) Glial cell line-derived neurotrophic factor receptor GFRalpha1 is expressed in the rat striatum during postnatal development. Brain Res Mol Brain Res 127:96–104PubMedCrossRefGoogle Scholar
  40. Chung CY, Seo H, Sonntag KC, Brooks A, Lin L, Isacson O (2005) Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Hum Mol Genet 14:1709–1725PubMedCrossRefGoogle Scholar
  41. Cintra A, Cao YH, Oellig C, Tinner B, Bortolotti F, Goldstein M, Pettersson RF, Fuxe K (1991) Basic FGF is present in dopaminergic neurons of the ventral midbrain of the rat. Neuroreport 2: 597–600PubMedCrossRefGoogle Scholar
  42. Colasanti M, Persichini T, Fabrizi C, Cavalieri E, Venturini G, Ascenzi P, Lauro GM, Suzuki H (1998) Expression of a NOS-III-like protein in human astroglial cell culture. Biochem Biophys Res Commun 252:552–555PubMedCrossRefGoogle Scholar
  43. Conn PJ, Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205–237PubMedCrossRefGoogle Scholar
  44. Counihan TJ, Landwehrmeyer GB, Standaert DG, Kosinski CM, Scherzer CR, Daggett LP, Velicelebi G, Young AB, Penney JB Jr (1998) Expression of N-methyl-D-aspartate receptor subunit mRNA in the human brain: mesencephalic dopaminergic neurons. J Comp Neurol 390:91–101PubMedCrossRefGoogle Scholar
  45. Crawley JN (1991) Cholecystokinin-dopamine interactions. Trends Pharmacol Sci 12:232–236PubMedCrossRefGoogle Scholar
  46. Creutz LM, Kritzer MF (2004) Mesostriatal and mesolimbic projections of midbrain neurons immunoreactive for estrogen receptor beta or androgen receptors in rats. J Comp Neurol 476:348–362PubMedCrossRefGoogle Scholar
  47. Dahlstrom A, Fuxe K (1964) Localization of monoamines in the lower brain stem. Experientia 20:398–399PubMedCrossRefGoogle Scholar
  48. Damier P, Hirsch EC, Agid Y, Graybiel AM (1999a) The substantia nigra of the human brain. I. Nigrosomes and the nigral matrix, a compartmental organization based on calbindin D(28K) immunohistochemistry. Brain 122(Pt 8):1421–1436CrossRefGoogle Scholar
  49. Damier P, Hirsch EC, Agid Y, Graybiel AM (1999b) The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease. Brain 122(Pt 8):1437–1448CrossRefGoogle Scholar
  50. Davila V, Yan Z, Craciun LC, Logothetis D, Sulzer D (2003) D3 dopamine autoreceptors do not activate G-protein-gated inwardly rectifying potassium channel currents in substantia nigra dopamine neurons. J Neurosci 23:5693–5697PubMedGoogle Scholar
  51. Dawson L, Chadha A, Megalou M, Duty S (2000) The group II metabotropic glutamate receptor agonist, DCG-IV, alleviates akinesia following intranigral or intraventricular administration in the reserpine-treated rat. Br J Pharmacol 129:541–546PubMedCrossRefGoogle Scholar
  52. Del Castillo J, Katz B (1955) The membrane potential changes in the frog’s heart produced by inhibitory nerve impulses. Nature 175:1035CrossRefGoogle Scholar
  53. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285PubMedCrossRefGoogle Scholar
  54. Di Chiara G, Porceddu ML, Morelli M, Mulas ML, Gessa GL (1979) Evidence for a GABAergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat. Brain Res 176:273–284PubMedCrossRefGoogle Scholar
  55. Diaz J, Levesque D, Lammers CH, Griffon N, Martres MP, Schwartz JC, Sokoloff P (1995) Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain. Neuroscience 65:731–745PubMedCrossRefGoogle Scholar
  56. Diaz J, Pilon C, Le Foll B, Gros C, Triller A, Schwartz JC, Sokoloff P (2000) Dopamine D3 receptors expressed by all mesencephalic dopamine neurons. J Neurosci 20:8677–8684PubMedGoogle Scholar
  57. Doherty M, Gratton A (2007) Differential involvement of ventral tegmental GABA(A) and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress. Brain Res 1150:62–68PubMedCrossRefGoogle Scholar
  58. Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, Triarhou LC, Chernet E, Perry KW, Nelson DL, Luecke S, Phebus LA, Bymaster FP, Paul SM (2001) Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA 98:14669–14674PubMedCrossRefGoogle Scholar
  59. Du F, Li R, Huang Y, Li X, Le W (2005) Dopamine D3 receptor-preferring agonists induce neurotrophic effects on mesencephalic dopamine neurons. Eur J Neurosci 22:2422–2430PubMedCrossRefGoogle Scholar
  60. Dun NJ, Dun SL, Forstermann U (1994) Nitric oxide synthase immunoreactivity in rat pontine medullary neurons. Neuroscience 59:429–445PubMedCrossRefGoogle Scholar
  61. Eliasson MJ, Blackshaw S, Schell MJ, Snyder SH (1997) Neuronal nitric oxide synthase alternatively spliced forms: prominent functional localizations in the brain. Proc Natl Acad Sci USA 94: 3396–3401PubMedCrossRefGoogle Scholar
  62. Esclapez M, Tillakaratne NJ, Tobin AJ, Houser CR (1993) Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. J Comp Neurol 331:339–362PubMedCrossRefGoogle Scholar
  63. Esclapez M, Tillakaratne NJ, Kaufman DL, Tobin AJ, Houser CR (1994) Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. J Neurosci 14: 1834–1855PubMedGoogle Scholar
  64. Falck B, Hillarp NA, Thieme G, Torp A (1962) Fluorescence of catecholamines and related compounds condensed with formaldehyde. J Histochem Cytochem 10:348–354Google Scholar
  65. Fallon JH, Loughlin SE (1982) Monoamine innervation of the forebrain: collateralization. Brain Res Bull 9:295–307PubMedCrossRefGoogle Scholar
  66. Fallon JH, Hicks R, Loughlin SE (1983) The origin of cholecystokinin terminals in the basal forebrain of the rat: evidence from immunofluorescence and retrograde tracing. Neurosci Lett 37:29–35PubMedCrossRefGoogle Scholar
  67. Faull RL, Mehler WR (1978) The cells of origin of nigrotectal, nigrothalamic and nigrostriatal projections in the rat. Neuroscience 3:989–1002PubMedCrossRefGoogle Scholar
  68. Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114(Pt 5):2283–2301PubMedCrossRefGoogle Scholar
  69. Ferraro L, Tomasini MC, Mazza R, Fuxe K, Fournier J, Tanganelli S, Antonelli T (2007) Neurotensin receptors as modulators of glutamatergic transmission. Brain Res RevGoogle Scholar
  70. Fibiger HC, Pudritz RE, McGeer PL, McGeer EG (1972) Axonal transport in nigro-striatal neurones. Nat New Biol 237:177–179PubMedCrossRefGoogle Scholar
  71. Flores C, Rodaros D, Stewart J (1998) Long-lasting induction of astrocytic basic fibroblast growth factor by repeated injections of amphetamine: blockade by concurrent treatment with a glutamate antagonist. J Neurosci 18:9547–9555PubMedGoogle Scholar
  72. Forster GL, Blaha CD (2003) Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci 17:751–762PubMedCrossRefGoogle Scholar
  73. Fortin M, Parent A (1996) Calretinin as a marker of specific neuronal subsets in primate substantia nigra and subthalamic nucleus. Brain Res 708:201–204PubMedCrossRefGoogle Scholar
  74. Galea E, Golanov EV, Feinstein DL, Kobylarz KA, Glickstein SB, Reis DJ (1998) Cerebellar stimulation reduces inducible nitric oxide synthase expression and protects brain from ischemia. Am J Physiol 274:H2035–H2045PubMedGoogle Scholar
  75. Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14:60–67PubMedCrossRefGoogle Scholar
  76. Gasmi M, Herzog CD, Brandon EP, Cunningham JJ, Ramirez GA, Ketchum ET, Bartus RT (2007) Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson’s disease. Mol Ther 15:62–68PubMedCrossRefGoogle Scholar
  77. Gatto EM, Riobo NA, Carreras MC, Chernavsky A, Rubio A, Satz ML, Poderoso JJ (2000) Overexpression of neutrophil neuronal nitric oxide synthase in Parkinson’s disease. Nitric Oxide 4:534–539PubMedCrossRefGoogle Scholar
  78. Geiger JR, Melcher T, Koh DS, Sakmann B, Seeburg PH, Jonas P, Monyer H (1995) Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15:193–204PubMedCrossRefGoogle Scholar
  79. Geisler S, Berod A, Zahm DS, Rostene W (2006) Brain neurotensin, psychostimulants, and stress–emphasis on neuroanatomical substrates. Peptides 27:2364–2384PubMedCrossRefGoogle Scholar
  80. Gerfen CR, Baimbridge KG, Miller JJ (1985) The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Natl Acad Sci USA 82:8780–8784PubMedCrossRefGoogle Scholar
  81. Gerfen CR, Baimbridge KG, Thibault J (1987a) The neostriatal mosaic: III. Biochemical and developmental dissociation of patch-matrix mesostriatal systems. J Neurosci 7:3935–3944PubMedGoogle Scholar
  82. Gerfen CR, Herkenham M, Thibault J (1987b) The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci 7:3915–3934PubMedGoogle Scholar
  83. German DC, Manaye K, Smith WK, Woodward DJ, Saper CB (1989) Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann Neurol 26:507–514PubMedCrossRefGoogle Scholar
  84. German DC, Manaye KF, Sonsalla PK, Brooks BA (1992) Midbrain dopaminergic cell loss in Parkinson’s disease and MPTP-induced parkinsonism: sparing of calbindin-D28k-containing cells. Ann NY Acad Sci 648:42–62PubMedCrossRefGoogle Scholar
  85. Geula C, Schatz CR, Mesulam MM (1993) Differential localization of NADPH-diaphorase and calbindin-D28k within the cholinergic neurons of the basal forebrain, striatum and brainstem in the rat, monkey, baboon and human. Neuroscience 54:461–476PubMedCrossRefGoogle Scholar
  86. Gibb WR (1992) Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson’s disease. Brain Res 581:283–291PubMedCrossRefGoogle Scholar
  87. Gibb WR, Lees AJ (1991) Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson’s disease. J Neurol Neurosurg Psychiatry 54:388–396PubMedCrossRefGoogle Scholar
  88. Golden JP, Baloh RH, Kotzbauer PT, Lampe PA, Osborne PA, Milbrandt J, Johnson EM Jr (1998) Expression of neurturin, GDNF, and their receptors in the adult mouse CNS. J Comp Neurol 398:139–150PubMedCrossRefGoogle Scholar
  89. Golembiowska K, Konieczny J, Ossowska K, Wolfarth S (2002) The role of striatal metabotropic glutamate receptors in degeneration of dopamine neurons: review article. Amino Acids 23:199–205PubMedCrossRefGoogle Scholar
  90. Gonzalez-Hernandez T, Rodriguez M (2000) Compartmental organization and chemical profile of dopaminergic and GABAergic neurons in the substantia nigra of the rat. J Comp Neurol 421:107–135PubMedCrossRefGoogle Scholar
  91. Gonzalez-Hernandez T, Perez de la Cruz MA, Mantolan-Sarmiento B (1996) Histochemical and immunohistochemical detection of neurons that produce nitric oxide: effect of different fixative parameters and immunoreactivity against non-neuronal NOS antisera. J Histochem Cytochem 44:1399–1413PubMedGoogle Scholar
  92. Gonzalez-Hernandez T, Abdala P, Rodriguez M (1997) NOS expression in nigral cells after excitotoxic and non-excitotoxic lesion of the pedunculopontine tegmental nucleus. Eur J Neurosci 9: 2658–2667PubMedCrossRefGoogle Scholar
  93. Gonzalez-Hernandez T, Barroso-Chinea P, Acevedo A, Salido E, Rodriguez M (2001) Colocalization of tyrosine hydroxylase and GAD65 mRNA in mesostriatal neurons. Eur J Neurosci 13:57–67PubMedCrossRefGoogle Scholar
  94. Gonzalez-Hernandez T, Barroso-Chinea P, De La Cruz Muros I, Del Mar Perez-Delgado M, Rodriguez M (2004) Expression of dopamine and vesicular monoamine transporters and differential vulnerability of mesostriatal dopaminergic neurons. J Comp Neurol 479:198–215PubMedCrossRefGoogle Scholar
  95. Goto S, Hirano A, Matsumoto S (1989) Subdivisional involvement of nigrostriatal loop in idiopathic Parkinson’s disease and striatonigral degeneration. Ann Neurol 26:766–770PubMedCrossRefGoogle Scholar
  96. Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4:2877–2890PubMedGoogle Scholar
  97. Greene JG (2006) Gene expression profiles of brain dopamine neurons and relevance to neuropsychiatric disease. J Physiol 575:411–416PubMedCrossRefGoogle Scholar
  98. Greene JG, Dingledine R, Greenamyre JT (2005) Gene expression profiling of rat midbrain dopamine neurons: implications for selective vulnerability in parkinsonism. Neurobiol Dis 18:19–31PubMedCrossRefGoogle Scholar
  99. Grofova I, Deniau JM, Kitai ST (1982) Morphology of the substantia nigra pars reticulata projection neurons intracellularly labeled with HRP. J Comp Neurol 208:352–368PubMedCrossRefGoogle Scholar
  100. Guix FX, Uribesalgo I, Coma M, Munoz FJ (2005) The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 76:126–152PubMedCrossRefGoogle Scholar
  101. Haber SN, Ryoo H, Cox C, Lu W (1995) Subsets of midbrain dopaminergic neurons in monkeys are distinguished by different levels of mRNA for the dopamine transporter: comparison with the mRNA for the D2 receptor, tyrosine hydroxylase and calbindin immunoreactivity. J Comp Neurol 362:400–410PubMedCrossRefGoogle Scholar
  102. Hall AV, Antoniou H, Wang Y, Cheung AH, Arbus AM, Olson SL, Lu WC, Kau CL, Marsden PA (1994) Structural organization of the human neuronal nitric oxide synthase gene (NOS1). J Biol Chem 269:33082–33090PubMedGoogle Scholar
  103. Hassler R (1938) Zur pathologie der paralysis agitans und des postencephalitschen Parkinsonismus. J Psychol Neurol 48:387–476Google Scholar
  104. Hattori T, Takada M, Moriizumi T, Van der Kooy D (1991) Single dopaminergic nigrostriatal neurons form two chemically distinct synaptic types: possible transmitter segregation within neurons. J Comp Neurol 309:391–401PubMedCrossRefGoogle Scholar
  105. Hedou G, Chasserot-Golaz S, Kemmel V, Gobaille S, Roussel G, Artault JC, Andriamampandry C, Aunis D, Maitre M (2000) Immunohistochemical studies of the localization of neurons containing the enzyme that synthesizes dopamine, GABA, or gamma-hydroxybutyrate in the rat substantia nigra and striatum. J Comp Neurol 426:549–560PubMedCrossRefGoogle Scholar
  106. Heimer L (2003) A new anatomical framework for neuropsychiatric disorders and drug abuse. Am J Psychiatry 160:1726–1739PubMedCrossRefGoogle Scholar
  107. Heizmann CW, Braun K (1992) Changes in Ca(2+)-binding proteins in human neurodegenerative disorders. Trends Neurosci 15:259–264PubMedCrossRefGoogle Scholar
  108. Herkenham M, Edley SM, Stuart J (1984) Cell clusters in the nucleus accumbens of the rat, and the mosaic relationship of opiate receptors, acetylcholinesterase and subcortical afferent terminations. Neuroscience 11:561–593PubMedCrossRefGoogle Scholar
  109. Hille B (1992) G protein-coupled mechanisms and nervous signaling. Neuron 9:187–195PubMedCrossRefGoogle Scholar
  110. Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84:5976–5980PubMedCrossRefGoogle Scholar
  111. Hirsch E, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature 334:345–348PubMedCrossRefGoogle Scholar
  112. Hokfelt T, Rehfeld JF, Skirboll L, Ivemark B, Goldstein M, Markey K (1980) Evidence for coexistence of dopamine and CCK in meso-limbic neurones. Nature 285:476–478PubMedCrossRefGoogle Scholar
  113. Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108PubMedCrossRefGoogle Scholar
  114. Horger BA, Nishimura MC, Armanini MP, Wang LC, Poulsen KT, Rosenblad C, Kirik D, Moffat B, Simmons L, Johnson E Jr, Milbrandt J, Rosenthal A, Bjorklund A, Vandlen RA, Hynes MA, Phillips HS (1998) Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 18: 4929–4937PubMedGoogle Scholar
  115. Huang EJ, Reichardt LF (2003) Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 72:609–642PubMedCrossRefGoogle Scholar
  116. Hubert GW, Paquet M, Smith Y (2001) Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey Substantia nigra. J Neurosci 21:1838–1847PubMedGoogle Scholar
  117. Hung HC, Lee EH (1996) The mesolimbic dopaminergic pathway is more resistant than the nigrostriatal dopaminergic pathway to MPTP and MPP+ toxicity: role of BDNF gene expression. Brain Res Mol Brain Res 41:14–26PubMedCrossRefGoogle Scholar
  118. Hunot S, Boissiere F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch EC (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience 72:355–363PubMedCrossRefGoogle Scholar
  119. Hurd YL, Pristupa ZB, Herman MM, Niznik HB, Kleinman JE (1994) The dopamine transporter and dopamine D2 receptor messenger RNAs are differentially expressed in limbic- and motor-related subpopulations of human mesencephalic neurons. Neuroscience 63:357–362PubMedCrossRefGoogle Scholar
  120. Hutter OF, Trautwein W (1955) Vagal and sympathetic effects on the pacemarker fibers in the sinus venous of the heart. J Gen Physiol 39:715–733CrossRefGoogle Scholar
  121. Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232PubMedCrossRefGoogle Scholar
  122. Iadecola C, Xu X, Zhang F, el-Fakahany EE, Ross ME (1995) Marked induction of calcium-independent nitric oxide synthase activity after focal cerebral ischemia. J Cereb Blood Flow Metab 15:52–59PubMedGoogle Scholar
  123. Iida M, Miyazaki I, Tanaka K, Kabuto H, Iwata-Ichikawa E, Ogawa N (1999) Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res 838: 51–59PubMedCrossRefGoogle Scholar
  124. Ikarashi Y, Yuzurihara M, Takahashi A, Hirohisa I, Shiobara T, Maruyama Y (1999) Modulation of acetylcholine release via GABAA and GABAB receptors in rat striatum. Brain Res 816:238–240PubMedCrossRefGoogle Scholar
  125. Ikura M, Osawa M, Ames JB (2002) The role of calcium-binding proteins in the control of transcription: structure to function. Bioessays 24:625–636PubMedCrossRefGoogle Scholar
  126. Inanobe A, Yoshimoto Y, Horio Y, Morishige KI, Hibino H, Matsumoto S, Tokunaga Y, Maeda T, Hata Y, Takai Y, Kurachi Y (1999) Characterization of G-protein-gated K+ channels composed of Kir3.2 subunits in dopaminergic neurons of the substantia nigra. J Neurosci 19:1006–1017PubMedGoogle Scholar
  127. Innis RB, Aghajanian GK (1987) Pertussis toxin blocks 5-HT1A and GABAB receptor-mediated inhibition of serotonergic neurons. Eur J Pharmacol 143:195–204PubMedCrossRefGoogle Scholar
  128. Iravani MM, Haddon CO, Cooper JM, Jenner P, Schapira AH (2006) Pramipexole protects against MPTP toxicity in non-human primates. J Neurochem 96:1315–1321PubMedCrossRefGoogle Scholar
  129. Iribe Y, Moore K, Pang KC, Tepper JM (1999) Subthalamic stimulation-induced synaptic responses in substantia nigra pars compacta dopaminergic neurons in vitro. J Neurophysiol 82:925–933PubMedGoogle Scholar
  130. Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW, Fox GM (1996) GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 85:1113–1124PubMedCrossRefGoogle Scholar
  131. Joel D, Weiner I (2000) The connections of the dopaminergic system with the striatum in rats and primates: an analysis with respect to the functional and compartmental organization of the striatum. Neuroscience 96:451–474PubMedCrossRefGoogle Scholar
  132. Joyce JN, Millan MJ (2007) Dopamine D3 receptor agonists for protection and repair in Parkinson’s disease. Curr Opin Pharmacol 7:100–105PubMedCrossRefGoogle Scholar
  133. Joyce JN, Woolsey C, Ryoo H, Borwege S, Hagner D (2004) Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson’s disease, and downregulates the dopamine transporter via the D3 receptor. BMC Biol 2:22PubMedCrossRefGoogle Scholar
  134. Kanno K, Hirata Y, Imai T, Marumo F (1993) Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells. Hypertension 22:34–39PubMedGoogle Scholar
  135. Kaplan DR, Miller FD (2000) Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10:381–391PubMedCrossRefGoogle Scholar
  136. Kaufman DL, Houser CR, Tobin AJ (1991) Two forms of the gamma-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem 56:720–723PubMedCrossRefGoogle Scholar
  137. Kerchner GA, Wang GD, Qiu CS, Huettner JE, Zhuo M (2001) Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism. Neuron 32: 477–488PubMedCrossRefGoogle Scholar
  138. Kobzik L, Reid MB, Bredt DS, Stamler JS (1994) Nitric oxide in skeletal muscle. Nature 372:546–548PubMedCrossRefGoogle Scholar
  139. Konitsiotis S, Blanchet PJ, Verhagen L, Lamers E, Chase TN (2000) AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology 54:1589–1595PubMedGoogle Scholar
  140. Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Deglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290:767–773PubMedCrossRefGoogle Scholar
  141. Kordower JH, Herzog CD, Dass B, Bakay RA, Stansell J 3rd, Gasmi M, Bartus RT (2006) Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Ann Neurol 60:706–715PubMedCrossRefGoogle Scholar
  142. Korotkova TM, Ponomarenko AA, Haas HL, Sergeeva OA (2005) Differential expression of the homeobox gene Pitx3 in midbrain dopaminergic neurons. Eur J Neurosci 22:1287–1293PubMedCrossRefGoogle Scholar
  143. Kosinski CM, Standaert DG, Testa CM, Penney JB Jr, Young AB (1998) Expression of metabotropic glutamate receptor 1 isoforms in the substantia nigra pars compacta of the rat. Neuroscience 86:783–798PubMedCrossRefGoogle Scholar
  144. Kotzbauer PT, Lampe PA, Heuckeroth RO, Golden JP, Creedon DJ, Johnson EM Jr, Milbrandt J (1996) Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 384:467–470PubMedCrossRefGoogle Scholar
  145. Kritzer MF (1997) Selective colocalization of immunoreactivity for intracellular gonadal hormone receptors and tyrosine hydroxylase in the ventral tegmental area, substantia nigra, and retrorubral fields in the rat. J Comp Neurol 379:247–260PubMedCrossRefGoogle Scholar
  146. Kubis N, Faucheux BA, Ransmayr G, Damier P, Duyckaerts C, Henin D, Forette B, Le Charpentier Y, Hauw JJ, Agid Y, Hirsch EC (2000) Preservation of midbrain catecholaminergic neurons in very old human subjects. Brain 123(Pt 2):366–373PubMedCrossRefGoogle Scholar
  147. Lacey MG (1993) Neurotransmitter receptors and ionic conductances regulating the activity of neurones in substantia nigra pars compacta and ventral tegmental area. Prog Brain Res 99:251–276PubMedCrossRefGoogle Scholar
  148. Lacey MG, Mercuri NB, North RA (1987) Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J Physiol 392:397–416PubMedGoogle Scholar
  149. Lacey MG, Mercuri NB, North RA (1988) On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. J Physiol 401:437–453PubMedGoogle Scholar
  150. Lamballe F, Klein R, Barbacid M (1991) trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell 66:967–979PubMedCrossRefGoogle Scholar
  151. Law SW, Conneely OM, DeMayo FJ, O’Malley BW (1992) Identification of a new brain-specific transcription factor, NURR1. Mol Endocrinol 6:2129–2135PubMedCrossRefGoogle Scholar
  152. Levivier M, Przedborski S, Bencsics C, Kang UJ (1995) Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease. J Neurosci 15:7810–7820PubMedGoogle Scholar
  153. Li H, He Z, Su T, Ma Y, Lu S, Dai C, Sun M (2003) Protective action of recombinant neurturin on dopaminergic neurons in substantia nigra in a rhesus monkey model of Parkinson’s disease. Neurol Res 25:263–267PubMedCrossRefGoogle Scholar
  154. Liang CL, Sinton CM, German DC (1996) Midbrain dopaminergic neurons in the mouse: co-localization with Calbindin-D28K and calretinin. Neuroscience 75:523–533PubMedCrossRefGoogle Scholar
  155. Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease.*********. Nat Med 5:1403–1409PubMedCrossRefGoogle Scholar
  156. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132PubMedCrossRefGoogle Scholar
  157. Lingor P, Unsicker K, Krieglstein K (2000) GDNF and NT-4 protect midbrain dopaminergic neurons from toxic damage by iron and nitric oxide. Exp Neurol 163:55–62PubMedCrossRefGoogle Scholar
  158. Loewi O (1921) Über humorale Übertragbarkeit der Hernervenwirking. Pflügers Arch 189:239–242CrossRefGoogle Scholar
  159. Lolova IS, Lolov SR (1995) Age-related changes in basic fibroblast growth factor-immunoreactive cells of rat substantia nigra. Mech Ageing Dev 82:73–89PubMedCrossRefGoogle Scholar
  160. Mark MD, Herlitze S (2000) G-protein mediated gating of inward-rectifier K+ channels. Eur J Biochem 267:5830–5836PubMedCrossRefGoogle Scholar
  161. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT (1993) Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 268:17478–17488PubMedGoogle Scholar
  162. Martin DL, Martin SB, Wu SJ, Espina N (1991) Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain. J Neurosci 11:2725–2731PubMedGoogle Scholar
  163. Martin LJ, Blackstone CD, Huganir RL, Price DL (1992) Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron 9:259–270PubMedCrossRefGoogle Scholar
  164. Matsuo I, Kuratani S, Kimura C, Takeda N, Aizawa S (1995) Mouse Otx2 functions in the formation and patterning of rostral head. Genes Dev 9:2646–2658PubMedCrossRefGoogle Scholar
  165. Mayfield RD, Zahniser NR (2001) Dopamine D2 receptor regulation of the dopamine transporter expressed in Xenopus laevis oocytes is voltage-independent. Mol Pharmacol 59:113–121PubMedGoogle Scholar
  166. McRitchie DA, Halliday GM (1995) Calbindin D28k-containing neurons are restricted to the medial substantia nigra in humans. Neuroscience 65:87–91PubMedCrossRefGoogle Scholar
  167. McRitchie DA, Hardman CD, Halliday GM (1996) Cytoarchitectural distribution of calcium binding proteins in midbrain dopaminergic regions of rats and humans. J Comp Neurol 364:121–150PubMedCrossRefGoogle Scholar
  168. McRitchie DA, Cartwright H, Pond SM, van der Schyf CJ, Castagnoli N Jr, van der Nest DG, Halliday GM (1998) The midbrain dopaminergic cell groups in the baboon Papio ursinus. Brain Res Bull 47:611–623PubMedCrossRefGoogle Scholar
  169. Meeley MP, Martin DL (1983) Inactivation of brain glutamate decarboxylase and the effects of adenosine 5’-triphosphate and inorganic phosphate. Cell Mol Neurobiol 3:39–54PubMedCrossRefGoogle Scholar
  170. Mendez I, Sanchez-Pernaute R, Cooper O, Vinuela A, Ferrari D, Bjorklund L, Dagher A, Isacson O (2005) Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson’s disease. Brain 128:1498–1510PubMedCrossRefGoogle Scholar
  171. Mendez I, Vinuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski JQ, Isacson O (2008) Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat Med 14: 507–509PubMedCrossRefGoogle Scholar
  172. Mercugliano M, Soghomonian JJ, Qin Y, Nguyen HQ, Feldblum S, Erlander MG, Tobin AJ, Chesselet MF (1992) Comparative distribution of messenger RNAs encoding glutamic acid decarboxylases (Mr 65,000 and Mr 67,000) in the basal ganglia of the rat. J Comp Neurol 318:245–254PubMedCrossRefGoogle Scholar
  173. Millan MJ, Seguin L, Gobert A, Cussac D, Brocco M (2004) The role of dopamine D3 compared with D2 receptors in the control of locomotor activity: a combined behavioural and neurochemical analysis with novel, selective antagonists in rats. Psychopharmacology (Berl) 174:341–357CrossRefGoogle Scholar
  174. Miller LP, Martin DL, Mazumder A, Walters JR (1978) Studies on the regulation of GABA synthesis: substrate-promoted dissociation of pyridoxal-5’-phosphate from GAD. J Neurochem 30:361–369PubMedCrossRefGoogle Scholar
  175. Miller GW, Gainetdinov RR, Levey AI, Caron MG (1999) Dopamine transporters and neuronal injury. Trends Pharmacol Sci 20:424–429PubMedCrossRefGoogle Scholar
  176. Mitra SW, Hoskin E, Yudkovitz J, Pear L, Wilkinson HA, Hayashi S, Pfaff DW, Ogawa S, Rohrer SP, Schaeffer JM, McEwen BS, Alves SE (2003) Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha. Endocrinology 144:2055–2067PubMedCrossRefGoogle Scholar
  177. Mohammed NA, Abd El-Aleem S, Appleton I, Maklouf MM, Said M, McMahon RF (2003) Expression of nitric oxide synthase isoforms in human liver cirrhosis. J Pathol 200:647–655PubMedCrossRefGoogle Scholar
  178. Moore RY, Bhatnagar RK, Heller A (1971) Anatomical and chemical studies of a nigro-neostriatal projection in the cat. Brain Res 30:119–135PubMedCrossRefGoogle Scholar
  179. Muramatsu Y, Kurosaki R, Watanabe H, Michimata M, Matsubara M, Imai Y, Araki T (2003) Cerebral alterations in a MPTP-mouse model of Parkinson’s disease–an immunocytochemical study. J Neural Transm 110:1129–1144PubMedCrossRefGoogle Scholar
  180. Murer G, Adelbrecht C, Lauritzen I, Lesage F, Lazdunski M, Agid Y, Raisman-Vozari R (1997) An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain. Neuroscience 80:345–357PubMedCrossRefGoogle Scholar
  181. Nakamura M, Jang IS, Ishibashi H, Watanabe S, Akaike N (2003) Possible roles of kainate receptors on GABAergic nerve terminals projecting to rat substantia nigra dopaminergic neurons. J Neurophysiol 90:1662–1670PubMedCrossRefGoogle Scholar
  182. Nash JE, Hill MP, Brotchie JM (1999) Antiparkinsonian actions of blockade of NR2B-containing NMDA receptors in the reserpine-treated rat. Exp Neurol 155:42–48PubMedCrossRefGoogle Scholar
  183. Nemoto C, Hida T, Arai R (1999) Calretinin and calbindin-D28k in dopaminergic neurons of the rat midbrain: a triple-labeling immunohistochemical study. Brain Res 846:129–136PubMedCrossRefGoogle Scholar
  184. Numan S, Seroogy KB (1999) Expression of trkB and trkC mRNAs by adult midbrain dopamine neurons: a double-label in situ hybridization study. J Comp Neurol 403:295–308PubMedCrossRefGoogle Scholar
  185. Nunes I, Tovmasian LT, Silva RM, Burke RE, Goff SP (2003) Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc Natl Acad Sci USA 100:4245–4250PubMedCrossRefGoogle Scholar
  186. Offen D, Shtaif B, Hadad D, Weizman A, Melamed E, Gil-Ad I (2001) Protective effect of insulin-like-growth-factor-1 against dopamine-induced neurotoxicity in human and rodent neuronal cultures: possible implications for Parkinson’s disease. Neurosci Lett 316:129–132PubMedCrossRefGoogle Scholar
  187. Olanow CW (1992) A rationale for dopamine agonists as primary therapy for Parkinson’s disease. Can J Neurol Sci 19:108–112PubMedGoogle Scholar
  188. Olszewski J, Baxter D (1954) Cytoarchitecture of the human brain stem. Karger, BaselGoogle Scholar
  189. Palacios JM, Savasta M, Mengod G (1989) Does cholecystokinin colocalize with dopamine in the human substantia nigra? Brain Res 488:369–375PubMedCrossRefGoogle Scholar
  190. Paquet M, Tremblay M, Soghomonian JJ, Smith Y (1997) AMPA and NMDA glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey: an immunohistochemical and in situ hybridization study. J Neurosci 17:1377–1396PubMedGoogle Scholar
  191. Parsons LH, Schad CA, Justice JB Jr (1993) Co-administration of the D2 antagonist pimozide inhibits up-regulation of dopamine release and uptake induced by repeated cocaine. J Neurochem 60:376–379PubMedCrossRefGoogle Scholar
  192. Patel NK, Gill SS (2007) GDNF delivery for Parkinson’s disease. Acta Neurochir Suppl 97:135–154PubMedCrossRefGoogle Scholar
  193. Pisani A, Calabresi P, Centonze D, Bernardi G (1997) Activation of group III metabotropic glutamate receptors depresses glutamatergic transmission at corticostriatal synapse. Neuropharmacology 36:845–851PubMedCrossRefGoogle Scholar
  194. Pisani A, Bernardi G, Bonsi P, Centonze D, Giacomini P, Calabresi P (2000) Cell-type specificity of mGluR activation in striatal neuronal subtypes. Amino Acids 19:119–129PubMedCrossRefGoogle Scholar
  195. Pochon NA, Menoud A, Tseng JL, Zurn AD, Aebischer P (1997) Neuronal GDNF expression in the adult rat nervous system identified by in situ hybridization. Eur J Neurosci 9:463–471PubMedCrossRefGoogle Scholar
  196. Przedborski S, Jackson-Lewis V, Yokoyama R, Shibata T, Dawson VL, Dawson TM (1996) Role of neuronal nitric oxide in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Proc Natl Acad Sci USA 93:4565–4571PubMedCrossRefGoogle Scholar
  197. Quesada A, Micevych PE (2004) Estrogen interacts with the IGF-1 system to protect nigrostriatal dopamine and maintain motoric behavior after 6-hydroxdopamine lesions. J Neurosci Res 75:107–116PubMedCrossRefGoogle Scholar
  198. Quesada A, Romeo HE, Micevych P (2007) Distribution and localization patterns of estrogen receptor-beta and insulin-like growth factor-1 receptors in neurons and glial cells of the female rat substantia nigra: localization of ERbeta and IGF-1R in substantia nigra. J Comp Neurol 503:198–208PubMedCrossRefGoogle Scholar
  199. Quesada A, Lee BY, Micevych PE (2008) PI3 kinase/Akt activation mediates estrogen and IGF-1 nigral DA neuronal neuroprotection against a unilateral rat model of Parkinson’s disease. Dev Neurobiol 68:632–644PubMedCrossRefGoogle Scholar
  200. Quik M, Police S, He L, Di Monte DA, Langston JW (2000) Expression of D(3) receptor messenger RNA and binding sites in monkey striatum and substantia nigra after nigrostriatal degeneration: effect of levodopa treatment. Neuroscience 98:263–273PubMedCrossRefGoogle Scholar
  201. Rahman S, McBride WJ (2002) Involvement of GABA and cholinergic receptors in the nucleus accumbens on feedback control of somatodendritic dopamine release in the ventral tegmental area. J Neurochem 80:646–654PubMedCrossRefGoogle Scholar
  202. Rameau GA, Chiu LY, Ziff EB (2003) NMDA receptor regulation of nNOS phosphorylation and induction of neuron death. Neurobiol Aging 24:1123–1133PubMedCrossRefGoogle Scholar
  203. Rameau GA, Tukey DS, Garcin-Hosfield ED, Titcombe RF, Misra C, Khatri L, Getzoff ED, Ziff EB (2007) Biphasic coupling of neuronal nitric oxide synthase phosphorylation to the NMDA receptor regulates AMPA receptor trafficking and neuronal cell death. J Neurosci 27:3445–3455PubMedCrossRefGoogle Scholar
  204. Redgrave P, Marrow L, Dean P (1992) Topographical organization of the nigrotectal projection in rat: evidence for segregated channels. Neuroscience 50:571–595PubMedCrossRefGoogle Scholar
  205. Reiner A, Anderson KD (1993) Co-occurrence of gamma-aminobutyric acid, parvalbumin and the neurotensin-related neuropeptide LANT6 in pallidal, nigral and striatal neurons in pigeons and monkeys. Brain Res 624:317–325PubMedCrossRefGoogle Scholar
  206. Rhinn M, Dierich A, Shawlot W, Behringer RR, Le Meur M, Ang SL (1998) Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development 125:845–856PubMedGoogle Scholar
  207. Rodriguez M, Gonzalez-Hernandez T (1999) Electrophysiological and morphological evidence for a GABAergic nigrostriatal pathway. J Neurosci 19:4682–4694PubMedGoogle Scholar
  208. Rodriguez MC, Obeso JA, Olanow CW (1998) Subthalamic nucleus-mediated excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann Neurol 44:S175–S188PubMedGoogle Scholar
  209. Rodriguez M, Barroso-Chinea P, Abdala P, Obeso J, Gonzalez-Hernandez T (2001) Dopamine cell degeneration induced by intraventricular administration of 6-hydroxydopamine in the rat: similarities with cell loss in parkinson’s disease. Exp Neurol 169:163–181PubMedCrossRefGoogle Scholar
  210. Rodriguez-Moreno A, Sihra TS (2007) Metabotropic actions of kainate receptors in the CNS. J Neurochem 103:2121–2135PubMedCrossRefGoogle Scholar
  211. Rogers J, Khan M, Ellis J (1990) Calretinin and other CaBPs in the nervous system. Adv Exp Med Biol 269:195–203PubMedGoogle Scholar
  212. Ronken E, Mulder AH, Schoffelmeer AN (1993) Interacting presynaptic kappa-opioid and GABAA receptors modulate dopamine release from rat striatal synaptosomes. J Neurochem 61:1634–1639PubMedCrossRefGoogle Scholar
  213. Rothblat DS, Schneider JS (1997) Regionally specific effects of haloperidol and clozapine on dopamine reuptake in the striatum. Neurosci Lett 228:119–122PubMedCrossRefGoogle Scholar
  214. Roubert C, Spielewoy C, Soubrie P, Hamon M, Giros B, Betancur C (2004) Altered neurotensin mrna expression in mice lacking the dopamine transporter. Neuroscience 123:537–546PubMedCrossRefGoogle Scholar
  215. Sarabi A, Hoffer BJ, Olson L, Morales M (2001) GFRalpha-1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area. J Comp Neurol 441:106–117PubMedCrossRefGoogle Scholar
  216. Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De Mayo F, Burbach JP, Conneely OM (1998) Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA 95:4013–4018PubMedCrossRefGoogle Scholar
  217. Schalling M, Friberg K, Seroogy K, Riederer P, Bird E, Schiffmann SN, Mailleux P, Vanderhaeghen JJ, Kuga S, Goldstein M et al (1990) Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia. Proc Natl Acad Sci USA 87:8427–8431PubMedCrossRefGoogle Scholar
  218. Schein JC, Hunter DD, Roffler-Tarlov S (1998) Girk2 expression in the ventral midbrain, cerebellum, and olfactory bulb and its relationship to the murine mutation weaver. Dev Biol 204:432–450PubMedCrossRefGoogle Scholar
  219. Schneider JS, Yuwiler A, Markham CH (1987) Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP. Brain Res 411:144–150PubMedCrossRefGoogle Scholar
  220. Schulz JB, Matthews RT, Muqit MM, Browne SE, Beal MF (1995) Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice. J Neurochem 64:936–939PubMedCrossRefGoogle Scholar
  221. Seabrook GR, Howson W, Lacey MG (1991) Subpopulations of GABA-mediated synaptic potentials in slices of rat dorsal striatum are differentially modulated by presynaptic GABAB receptors. Brain Res 562:332–334PubMedCrossRefGoogle Scholar
  222. Seroogy K, Ceccatelli S, Schalling M, Hokfelt T, Frey P, Walsh J, Dockray G, Brown J, Buchan A, Goldstein M (1988) A subpopulation of dopaminergic neurons in rat ventral mesencephalon contains both neurotensin and cholecystokinin. Brain Res 455:88–98PubMedCrossRefGoogle Scholar
  223. Seroogy KB, Dangaran K, Lim S, Haycock JW, Fallon JH (1989) Ventral mesencephalic neurons containing both cholecystokinin- and tyrosine hydroxylase-like immunoreactivities project to forebrain regions. J Comp Neurol 279:397–414PubMedCrossRefGoogle Scholar
  224. Seroogy KB, Lundgren KH, Tran TM, Guthrie KM, Isackson PJ, Gall CM (1994) Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. J Comp Neurol 342:321–334PubMedCrossRefGoogle Scholar
  225. Shavali S, Ren J, Ebadi M (2003) Insulin-like growth factor-1 protects human dopaminergic SH-SY5Y cells from salsolinol-induced toxicity. Neurosci Lett 340:79–82PubMedCrossRefGoogle Scholar
  226. Shimada S, Kitayama S, Walther D, Uhl G (1992) Dopamine transporter mRNA: dense expression in ventral midbrain neurons. Brain Res Mol Brain Res 13:359–362PubMedCrossRefGoogle Scholar
  227. Singh S, Dikshit M (2007) Apoptotic neuronal death in Parkinson’s disease: involvement of nitric oxide. Brain Res Rev 54:233–250PubMedCrossRefGoogle Scholar
  228. Smidt MP, van Schaick HS, Lanctot C, Tremblay JJ, Cox JJ, van der Kleij AA, Wolterink G, Drouin J, Burbach JP (1997) A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc Natl Acad Sci USA 94:13305–13310PubMedCrossRefGoogle Scholar
  229. Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP (2000) A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci 3:337–341PubMedCrossRefGoogle Scholar
  230. Smidt MP, Smits SM, Burbach JP (2003) Molecular mechanisms underlying midbrain dopamine neuron development and function. Eur J Pharmacol 480:75–88PubMedCrossRefGoogle Scholar
  231. Smidt MP, Smits SM, Bouwmeester H, Hamers FP, van der Linden AJ, Hellemons AJ, Graw J, Burbach JP (2004a) Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development 131:1145–1155PubMedCrossRefGoogle Scholar
  232. Smidt MP, Smits SM, Burbach JP (2004b) Homeobox gene Pitx3 and its role in the development of dopamine neurons of the substantia nigra. Cell Tissue Res 318:35–43PubMedCrossRefGoogle Scholar
  233. Smith ID, Grace AA (1992) Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity. Synapse 12:287–303PubMedCrossRefGoogle Scholar
  234. Smith Y, Hazrati LN, Parent A (1990) Efferent projections of the subthalamic nucleus in the squirrel monkey as studied by the PHA-L anterograde tracing method. J Comp Neurol 294:306–323PubMedCrossRefGoogle Scholar
  235. Smith Y, Charara A, Paquet M, Kieval JZ, Pare JF, Hanson JE, Hubert GW, Kuwajima M, Levey AI (2001) Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia. J Chem Neuroanat 22:13–42PubMedCrossRefGoogle Scholar
  236. Smolders I, De Klippel N, Sarre S, Ebinger G, Michotte Y (1995) Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat. Eur J Pharmacol 284:83–91PubMedCrossRefGoogle Scholar
  237. Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP, Amara SG (1997) Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants. J Neurosci 17:960–974PubMedGoogle Scholar
  238. Sonsalla PK, Albers DS, Zeevalk GD (1998) Role of glutamate in neurodegeneration of dopamine neurons in several animal models of Parkinsonism. Amino Acids 14:69–74PubMedCrossRefGoogle Scholar
  239. Spink DC, Porter TG, Wu SJ, Martin DL (1985) Characterization of three kinetically distinct forms of glutamate decarboxylase from pig brain. Biochem J 231:695–703PubMedGoogle Scholar
  240. Tatoyan A, Giulivi C (1998) Purification and characterization of a nitric-oxide synthase from rat liver mitochondria. J Biol Chem 273:11044–11048PubMedCrossRefGoogle Scholar
  241. Thompson L, Barraud P, Andersson E, Kirik D, Bjorklund A (2005) Identification of dopaminergic neurons of nigral and ventral tegmental area subtypes in grafts of fetal ventral mesencephalon based on cell morphology, protein expression, and efferent projections. J Neurosci 25:6467–6477PubMedCrossRefGoogle Scholar
  242. Timmer M, Cesnulevicius K, Winkler C, Kolb J, Lipokatic-Takacs E, Jungnickel J, Grothe C (2007) Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine lesion. J Neurosci 27:459–471PubMedCrossRefGoogle Scholar
  243. Tooyama I, Kawamata T, Walker D, Yamada T, Hanai K, Kimura H, Iwane M, Igarashi K, McGeer EG, McGeer PL (1993) Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson’s disease. Neurology 43:372–376PubMedGoogle Scholar
  244. Tooyama I, McGeer EG, Kawamata T, Kimura H, McGeer PL (1994) Retention of basic fibroblast growth factor immunoreactivity in dopaminergic neurons of the substantia nigra during normal aging in humans contrasts with loss in Parkinson’s disease. Brain Res 656:165–168PubMedCrossRefGoogle Scholar
  245. Trupp M, Belluardo N, Funakoshi H, Ibanez CF (1997) Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS. J Neurosci 17:3554–3567PubMedGoogle Scholar
  246. Uhl GR, Walther D, Mash D, Faucheux B, Javoy-Agid F (1994) Dopamine transporter messenger RNA in Parkinson’s disease and control substantia nigra neurons. Ann Neurol 35:494–498PubMedCrossRefGoogle Scholar
  247. van den Munckhof P, Luk KC, Ste-Marie L, Montgomery J, Blanchet PJ, Sadikot AF, Drouin J (2003) Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development 130:2535–2542PubMedCrossRefGoogle Scholar
  248. van der Kooy D, Coscina DV, Hattori T (1981) Is there a non-dopaminergic nigrostriatal pathway? Neuroscience 6:345–357PubMedCrossRefGoogle Scholar
  249. Varastet M, Riche D, Maziere M, Hantraye P (1994) Chronic MPTP treatment reproduces in baboons the differential vulnerability of mesencephalic dopaminergic neurons observed in Parkinson’s disease. Neuroscience 63:47–56PubMedCrossRefGoogle Scholar
  250. Vernon AC, Zbarsky V, Datla KP, Dexter DT, Croucher MJ (2007) Selective activation of group III metabotropic glutamate receptors by L-(+)-2-amino-4-phosphonobutryic acid protects the nigrostriatal system against 6-hydroxydopamine toxicity in vivo. J Pharmacol Exp Ther 320:397–409PubMedCrossRefGoogle Scholar
  251. Walker DG, Terai K, Matsuo A, Beach TG, McGeer EG, McGeer PL (1998) Immunohistochemical analyses of fibroblast growth factor receptor-1 in the human substantia nigra. Comparison between normal and Parkinson’s disease cases. Brain Res 794:181–187PubMedCrossRefGoogle Scholar
  252. Wassef M, Joyner AL (1997) Early mesencephalon/metencephalon patterning and development of the cerebellum. Perspect Dev Neurobiol 5:3–16PubMedGoogle Scholar
  253. Weiss-Wunder LT, Chesselet MF (1991) Subpopulations of mesencephalic dopaminergic neurons express different levels of tyrosine hydroxylase messenger RNA. J Comp Neurol 303:478–488PubMedCrossRefGoogle Scholar
  254. Wigmore MA, Lacey MG (1998) Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat midbrain dopamine neurones in vitro. Br J Pharmacol 123:667–674PubMedCrossRefGoogle Scholar
  255. Wu T, Wang HL (1994) CCK-8 excites substantia nigra dopaminergic neurons by increasing a cationic conductance. Neurosci Lett 170:229–232PubMedCrossRefGoogle Scholar
  256. Wullner U, Standaert DG, Testa CM, Penney JB, Young AB (1997) Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain. Brain Res 768:215–223PubMedCrossRefGoogle Scholar
  257. Xu KY, Huso DL, Dawson TM, Bredt DS, Becker LC (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96:657–662PubMedCrossRefGoogle Scholar
  258. Yamada T, McGeer PL, Baimbridge KG, McGeer EG (1990) Relative sparing in Parkinson’s disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res 526:303–307PubMedCrossRefGoogle Scholar
  259. Ye W, Shimamura K, Rubenstein JL, Hynes MA, Rosenthal A (1998) FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93:755–766PubMedCrossRefGoogle Scholar
  260. Zahniser NR, Doolen S (2001) Chronic and acute regulation of Na+/Cl- -dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. Pharmacol Ther 92:21–55PubMedCrossRefGoogle Scholar
  261. Zapata A, Witkin JM, Shippenberg TS (2001) Selective D3 receptor agonist effects of (+)-PD 128907 on dialysate dopamine at low doses. Neuropharmacology 41:351–359PubMedCrossRefGoogle Scholar
  262. Zetterstrom RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T (1997) Dopamine neuron agenesis in Nurr1-deficient mice. Science 276:248–250PubMedCrossRefGoogle Scholar
  263. Zhao S, Maxwell S, Jimenez-Beristain A, Vives J, Kuehner E, Zhao J, O’Brien C, de Felipe C, Semina E, Li M (2004) Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons. Eur J Neurosci 19:1133–1140PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien Printed in Germany 2009

Authors and Affiliations

  • Tomás González-Hernández
    • 1
    Email author
  • Domingo Afonso-Oramas
    • 1
  • Ignacio Cruz-Muros
    • 1
  1. 1.Department of Anatomy, Faculty of MedicineUniversity of La LagunaLa LagunaSpain

Personalised recommendations