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Neurochemistry of the Sleep-Wake Cycle in Parkinson’s Disease

  • Chapter
Book cover Disorders of Sleep and Circadian Rhythms in Parkinson's Disease

Abstract

Many Parkinson’s disease (PD) patients struggle with excessive daytime sleepiness independent of their poor nocturnal sleep quality. Unexplained by comorbid conditions, these symptoms are inherent to the underlying neuropathology of the disease. Widespread neurodegeneration in PD affects multiple neurotransmitter systems critical for regulating the sleep-wake cycle including: dopamine, acetylcholine, hypocretin/orexin, serotonin, norepinephrine, and melanin-concentrating hormone. Disruptions in these interconnected signaling pathways reduce arousal through both direct and indirect (i.e., positive and negative feedback loops) mechanisms. This chapter reviews the role of each of these neurotransmitter systems in sleep-wake regulation and how degeneration of these nuclei may contribute to deficits in the sleep-wake cycle of PD patients.

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References

  1. Hogl B, Seppi K, Brandauer E, Glatzl S, Frauscher B, Niedermuller U, Wenning G, Poewe W. Increased daytime sleepiness in Parkinson’s disease: a questionnaire survey. Mov Disord. 2003;18(3):319–23.

    Article  PubMed  Google Scholar 

  2. Ondo WG, Vuong KV, Khan H, Atassi F, Kwak C, Jankovic J. Daytime sleepiness and other sleep disorders in Parkinson’s disease. Neurology. 2001;57:1392–6.

    Article  CAS  PubMed  Google Scholar 

  3. Tan EK, Lum SY, Fook-Chong SMC, Teoh ML, Yih Y, Tan L, Tan A, Wong MC. Evaluation of somnolence in Parkinson’s disease: comparison with age and sex matched controls. Neurology. 2002;58(3):465–8.

    Article  CAS  PubMed  Google Scholar 

  4. Arnulf I, Konofal E, Merino-Andreu M, Houeto JL, Mesnage V, Welter ML, Lacomblez L, Golmard JL, Derenne JP, Agid Y. Parkinson’s disease a sleepiness: an integral part of PD. Neurology. 2002;58:1019–24.

    Article  CAS  PubMed  Google Scholar 

  5. Rye DB, Bliwise DL, Dihenia B, Gurecki P. FAST TRACK: daytime sleepiness in Parkinson’s disease. J Sleep Res. 2000;9(1):63–9.

    Article  CAS  PubMed  Google Scholar 

  6. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001;21(5):1787–94.

    CAS  PubMed  Google Scholar 

  7. Kume K, Kume S, Park SK, Hirsh J, Jackson FR. Dopamine is a regulator of arousal in the fruit fly. J Neurosci. 2005;25(32):7377–84.

    Article  CAS  PubMed  Google Scholar 

  8. Trampus M, Ferri N, Adami M, Ongini E. The dopamine D1 receptor agonists, A68930 and SKF 38393, induce arousal and suppress REM sleep in the rat. Eur J Pharmacol. 1993;235(1):83–7.

    Article  CAS  PubMed  Google Scholar 

  9. Sakata M, Sei H, Toida K, Fujihara H, Urushihara R, Morita Y. Mesolimbic dopaminergic system is involved in diurnal blood pressure regulation. Brain Res. 2002;928(1–2):194–201.

    Article  CAS  PubMed  Google Scholar 

  10. Lu J, Jhou TC, Saper CB. Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J Neurosci. 2006;26(1):193–202.

    Article  CAS  PubMed  Google Scholar 

  11. Daley JT, Turner RS, Bliwise DL, Rye DB. Nocturnal sleep and daytime alertness in the MPTP-treated primate. Sleep. 1999;22(Suppl):S218–9.

    Google Scholar 

  12. Almirall H, Pigarev I, de la Calzada MD, Pigareva M, Herrero MT, Sagales T. Nocturnal sleep structure and temperature slope in MPTP treated monkeys. J Neural Transm. 1999;106(11–12):1125–34.

    Article  CAS  PubMed  Google Scholar 

  13. Trulson ME, Preussler DW, Howell GA. Activity of substantia nigra units across the sleep-waking cycle in freely moving cats. Neurosci Lett. 1981;26(2):183–8.

    Article  CAS  PubMed  Google Scholar 

  14. Gonon FG. Nonlinear relationship between impulse flow and dopamine released by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry. Neuroscience. 1988;24(1):19–28.

    Article  CAS  PubMed  Google Scholar 

  15. Chergui K, Akaoka H, Charlety PJ, Saunier CF, Buda M, Chouvet G. Subthalamic nucleus modulates burst firing of nigral dopamine neurones via NMDA receptors. Neuroreport. 1994;5(10):1185–8.

    Article  CAS  PubMed  Google Scholar 

  16. Kitai ST, Shepard PD, Callaway JC, Scroggs R. Afferent modulation of dopamine neuron firing patterns. Curr Opin Neurobiol. 1999;9(6):690–7.

    Article  CAS  PubMed  Google Scholar 

  17. Clarke PB, Hommer DW, Pert A, Skirboll LR. Innervation of substantia nigra neurons by cholinergic afferents from pedunculopontine nucleus in the rat: neuroanatomical and electrophysiological evidence. Neuroscience. 1987;23(3):1011–9.

    Article  CAS  PubMed  Google Scholar 

  18. Agid Y. Parkinson’s disease: pathophysiology. Lancet. 1991;337(8753):1321–4.

    Article  CAS  PubMed  Google Scholar 

  19. German DC, Manaye K, Smith WK, Woodward DJ, Saper CB. Midbrain dopaminergic cell loss in Parkinson’s disease: computer visualization. Ann Neurol. 1989;26(4):507–14.

    Article  CAS  PubMed  Google Scholar 

  20. Hirsch E, Graybiel AM, Agid YA. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature. 1988;334(6180):345–8.

    Article  CAS  PubMed  Google Scholar 

  21. Paulus W, Jellinger K. The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol. 1991;50(6):743–55.

    Article  CAS  PubMed  Google Scholar 

  22. Freeman A, Ciliax BJ, Bakay R, Daley J, Miller RD, Keating GL, Levey AI, Rye DB. Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models. Ann Neurol. 2001;50:321–9.

    Article  CAS  PubMed  Google Scholar 

  23. Beckstead RM, Domesick VB, Nauta WJ. Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res. 1979;175(2):191–217.

    Article  CAS  PubMed  Google Scholar 

  24. Pasquier DA, Kemper TL, Forbes WB, Morgane PJ. Dorsal raphe, substantia nigra and locus coeruleus: interconnections with each other and the neostriatum. Brain Res Bull. 1977;2(5):323–39.

    Article  CAS  PubMed  Google Scholar 

  25. Hallanger AE, Levey AI, Lee HJ, Rye DB, Wainer BH. The origins of cholinergic and other subcortical afferents to the thalamus in the rat. J Comp Neurol. 1987;262:105–24.

    Article  CAS  PubMed  Google Scholar 

  26. Semba K. Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat. J Comp Neurol. 1993;330(4):543–56.

    Article  CAS  PubMed  Google Scholar 

  27. Steriade M, Datta S, Pare D, Oakson G, Curro Dossi RC. Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems. J Neurosci. 1990;10(8):2541–59.

    CAS  PubMed  Google Scholar 

  28. Braak H, Tredici K, Rub U, de Vos R, Jansen Steur E, Braak E. Staging of brain pathology related to sproadic Parkinson’s disease. Neurobiol Aging. 2003;24:197–211.

    Article  PubMed  Google Scholar 

  29. Gaspar P, Gray F. Dementia in idiopathic Parkinson’s disease. A neuropathological study of 32 cases. Acta Neuropathol. 1984;64(1):43–52.

    Article  CAS  PubMed  Google Scholar 

  30. Tagliavini F, Pilleri G, Bouras C, Constantinidis J. The basal nucleus of Meynert in idiopathic Parkinson’s disease. Acta Neurol Scand. 1984;70(1):20–8.

    Article  CAS  PubMed  Google Scholar 

  31. Bohnen NI, Kaufer DI, Ivanco LS, Lopresti B, Koeppe RA, Davis JG, Mathis CA, Moore RY, DeKosky ST. Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol. 2003;60(12):1745–8.

    Article  PubMed  Google Scholar 

  32. Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL. The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol. 1989;26(1):41–6.

    Article  CAS  PubMed  Google Scholar 

  33. Kotagal V, Muller ML, Kaufer DI, Koeppe RA, Bohnen NI. Thalamic cholinergic innervation is spared in Alzheimer disease compared to parkinsonian disorders. Neurosci Lett. 2012;514(2):169–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Mazzone P, Lozano A, Stanzione P, Galati S, Scarnati E, Peppe A, Stefani A. Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson’s disease. Neuroreport. 2005;16(17):1877–81.

    Article  PubMed  Google Scholar 

  35. Alessandro S, Ceravolo R, Brusa L, Pierantozzi M, Costa A, Galati S, Placidi F, Romigi A, Iani C, Marzetti F, Peppe A. Non-motor functions in parkinsonian patients implanted in the pedunculopontine nucleus: focus on sleep and cognitive domains. J Neurol Sci. 2010;289:44–8.

    Article  PubMed  Google Scholar 

  36. Lim AS, Moro E, Lozano AM, Hamani C, Dostrovsky JO, Hutchison WD, Lang AE, Wennberg RA, Murray BJ. Selective enhancement of rapid eye movement sleep by deep brain stimulation of the human pons. Ann Neurol. 2009;66(1):110–4.

    Article  PubMed  Google Scholar 

  37. Arnulf I, Ferraye M, Fraix V, Benabid AL, Chabardes S, Goetz L, Pollak P, Debu B. Sleep induced by stimulation in the human pedunculopontine nucleus area. Ann Neurol. 2010;67(4):546–9.

    Article  PubMed  Google Scholar 

  38. Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, Sanchez-Valle R, Vilaseca I, Lomena F, Vilas D, Llado A, Gaig C, Santamaria J. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12(5):443–53.

    Article  PubMed  Google Scholar 

  39. Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013;14(8):744–8.

    Article  PubMed  Google Scholar 

  40. Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, Benarroch EE, Ahlskog JE, Smith GE, Caselli RC, Tippman-Peikert M, Olson EJ, Lin SC, Young T, Wszolek Z, Schenck CH, Mahowald MW, Castillo PR, Del Tredici K, Braak H. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007;130(Pt 11):2770–88.

    Article  CAS  PubMed  Google Scholar 

  41. Kim YK, Yoon IY, Kim JM, Jeong SH, Kim KW, Shin YK, Kim BS, Kim SE. The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder. Eur J Neurol. 2010;17(3):487–92.

    Article  CAS  PubMed  Google Scholar 

  42. Kotagal V, Albin RL, Muller ML, Koeppe RA, Chervin RD, Frey KA, Bohnen NI. Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease. Ann Neurol. 2012;71(4):560–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18(23):9996–10015.

    CAS  PubMed  Google Scholar 

  44. Hagan JJ, Leslie RA, Patel S, Evans ML, Wattam TA, Holmes S, Benham CD, Taylor SG, Routledge C, Hemmati P, Munton RP, Ashmeade TE, Shah AS, Hatcher JP, Hatcher PD, Jones DN, Smith MI, Piper DC, Hunter AJ, Porter RA, Upton N. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci U S A. 1999;96(19):10911–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett 2nd FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322–7.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573–85.

    Article  CAS  PubMed  Google Scholar 

  47. van den Pol AN. Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci. 1999;19(8):3171–82.

    PubMed  Google Scholar 

  48. Chou TC, Scammell TE, Gooley JJ, Gaus SE, Saper CB, Lu J. Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci. 2003;23(33):10691–702.

    CAS  PubMed  Google Scholar 

  49. Torrealba F, Yanagisawa M, Saper CB. Colocalization of orexin a and glutamate immunoreactivity in axon terminals in the tuberomammillary nucleus in rats. Neuroscience. 2003;119(4):1033–44.

    Article  CAS  PubMed  Google Scholar 

  50. Hassani OK, Lee MG, Jones BE. Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep-wake cycle. Proc Natl Acad Sci U S A. 2009;106(7):2418–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Mileykovskiy BY, Kiyashchenko LI, Siegel JM. Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron. 2005;46(5):787–98.

    Article  CAS  PubMed  Google Scholar 

  52. Eggermann E, Serafin M, Bayer L, Machard D, Saint-Mleux B, Jones BE, Muhlethaler M. Orexins/hypocretins excite basal forebrain cholinergic neurones. Neuroscience. 2001;108(2):177–81.

    Article  CAS  PubMed  Google Scholar 

  53. Burlet S, Tyler CJ, Leonard CS. Direct and indirect excitation of laterodorsal tegmental neurons by Hypocretin/Orexin peptides: implications for wakefulness and narcolepsy. J Neurosci. 2002;22(7):2862–72.

    CAS  PubMed  Google Scholar 

  54. Brown RE, Sergeeva OA, Eriksson KS, Haas HL. Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J Neurosci. 2002;22(20):8850–9.

    CAS  PubMed  Google Scholar 

  55. Eriksson KS, Sergeeva O, Brown RE, Haas HL. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J Neurosci. 2001;21(23):9273–9.

    CAS  PubMed  Google Scholar 

  56. Uramura K, Funahashi H, Muroya S, Shioda S, Takigawa M, Yada T. Orexin-a activates phospholipase C- and protein kinase C-mediated Ca2+ signaling in dopamine neurons of the ventral tegmental area. Neuroreport. 2001;12(9):1885–9.

    Article  CAS  PubMed  Google Scholar 

  57. Espana RA, Baldo BA, Kelley AE, Berridge CW. Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action. Neuroscience. 2001;106(4):699–715.

    Article  CAS  PubMed  Google Scholar 

  58. Bourgin P, Huitron-Resendiz S, Spier AD, Fabre V, Morte B, Criado JR, Sutcliffe JG, Henriksen SJ, de Lecea L. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci. 2000;20(20):7760–5.

    CAS  PubMed  Google Scholar 

  59. Xi MC, Morales FR, Chase MH. Effects on sleep and wakefulness of the injection of hypocretin-1 (orexin-A) into the laterodorsal tegmental nucleus of the cat. Brain Res. 2001;901(1–2):259–64.

    Article  CAS  PubMed  Google Scholar 

  60. Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450(7168):420–4.

    Article  CAS  PubMed  Google Scholar 

  61. Carter ME, Adamantidis A, Ohtsu H, Deisseroth K, de Lecea L. Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J Neurosci. 2009;29(35):10939–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Thannickal TC, Lai YY, Siegel JM. Hypocretin (orexin) cell loss in Parkinson’s disease. Brain. 2007;130(Pt 6):1586–95.

    Article  PubMed  Google Scholar 

  63. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27(3):469–74.

    Article  CAS  PubMed  Google Scholar 

  64. Wienecke M, Werth E, Poryazova R, Baumann-Vogel H, Bassetti CL, Weller M, Waldvogel D, Storch A, Baumann CR. Progressive dopamine and hypocretin deficiencies in Parkinson’s disease: is there an impact on sleep and wakefulness? J Sleep Res. 2012;21(6):710–7.

    Article  PubMed  Google Scholar 

  65. Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S, Mignot E, Shiromani PJ. Relationship between CSF hypocretin levels and hypocretin neuronal loss. Exp Neurol. 2003;184(2):1010–6.

    Article  CAS  PubMed  Google Scholar 

  66. Dahlstroem A, Fuxe K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl. 1964;Suppl 232:231–55.

    Google Scholar 

  67. Vertes RP, Fortin WJ, Crane AM. Projections of the median raphe nucleus in the rat. J Comp Neurol. 1999;407(4):555–82.

    Article  CAS  PubMed  Google Scholar 

  68. Chou TC, Bjorkum AA, Gaus SE, Lu J, Scammell TE, Saper CB. Afferents to the ventrolateral preoptic nucleus. J Neurosci. 2002;22(3):977–90.

    CAS  PubMed  Google Scholar 

  69. Vertes RP. A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J Comp Neurol. 1991;313(4):643–68.

    Article  CAS  PubMed  Google Scholar 

  70. McGinty DJ, Harper RM. Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res. 1976;101(3):569–75.

    Article  CAS  PubMed  Google Scholar 

  71. Meyer-Bernstein EL, Morin LP. Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J Neurosci. 1996;16(6):2097–111.

    CAS  PubMed  Google Scholar 

  72. Trulson ME, Jacobs BL. Raphe unit activity in freely moving cats: correlation with level of behavioral arousal. Brain Res. 1979;163(1):135–50.

    Article  CAS  PubMed  Google Scholar 

  73. Halliday GM, Blumbergs PC, Cotton RG, Blessing WW, Geffen LB. Loss of brainstem serotonin- and substance P-containing neurons in Parkinson’s disease. Brain Res. 1990;510(1):104–7.

    Article  CAS  PubMed  Google Scholar 

  74. Lindvall O, Bjorklund A. The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. Acta Physiol Scand Suppl. 1974;412:1–48.

    CAS  PubMed  Google Scholar 

  75. Yamanaka A, Muraki Y, Tsujino N, Goto K, Sakurai T. Regulation of orexin neurons by the monoaminergic and cholinergic systems. Biochem Biophys Res Commun. 2003;303(1):120–9.

    Article  CAS  PubMed  Google Scholar 

  76. Berridge CW, Isaac SO, Espana RA. Additive wake-promoting actions of medial basal forebrain noradrenergic alpha1- and beta-receptor stimulation. Behav Neurosci. 2003;117(2):350–9.

    Article  CAS  PubMed  Google Scholar 

  77. Hou YP, Manns ID, Jones BE. Immunostaining of cholinergic pontomesencephalic neurons for alpha 1 versus alpha 2 adrenergic receptors suggests different sleep-wake state activities and roles. Neuroscience. 2002;114(3):517–21.

    Article  CAS  PubMed  Google Scholar 

  78. Aston-Jones G, Bloom FE. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci. 1981;1(8):876–86.

    CAS  PubMed  Google Scholar 

  79. Carter ME, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S, Deisseroth K, de Lecea L. Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci. 2010;13(12):1526–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Mann DM. The locus coeruleus and its possible role in ageing and degenerative disease of the human central nervous system. Mech Ageing Dev. 1983;23(1):73–94.

    Article  CAS  PubMed  Google Scholar 

  81. Panula P, Pirvola U, Auvinen S, Airaksinen MS. Histamine-immunoreactive nerve fibers in the rat brain. Neuroscience. 1989;28(3):585–610.

    Article  CAS  PubMed  Google Scholar 

  82. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183–241.

    Article  CAS  PubMed  Google Scholar 

  83. Takahashi K, Lin JS, Sakai K. Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep states in the mouse. J Neurosci. 2006;26(40):10292–8.

    Article  CAS  PubMed  Google Scholar 

  84. Nakamura S, Ohnishi K, Nishimura M, Suenaga T, Akiguchi I, Kimura J, Kimura T. Large neurons in the tuberomammillary nucleus in patients with Parkinson’s disease and multiple system atrophy. Neurology. 1996;46(6):1693–6.

    Article  CAS  PubMed  Google Scholar 

  85. Rinne JO, Anichtchik OV, Eriksson KS, Kaslin J, Tuomisto L, Kalimo H, Roytta M, Panula P. Increased brain histamine levels in Parkinson’s disease but not in multiple system atrophy. J Neurochem. 2002;81(5):954–60.

    Article  CAS  PubMed  Google Scholar 

  86. Anichtchik OV, Rinne JO, Kalimo H, Panula P. An altered histaminergic innervation of the substantia nigra in Parkinson’s disease. Exp Neurol. 2000;163(1):20–30.

    Article  CAS  PubMed  Google Scholar 

  87. Arnulf I. Results of clinical trials of tiprolisant in narcolepsy and Parkinson’s disease. Eur Neuropsychopharmacol. 2009;19:S204.

    Article  Google Scholar 

  88. Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, Vale W, Sawchenko PE. The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol. 1992;319(2):218–45.

    Article  CAS  PubMed  Google Scholar 

  89. Bayer L, Mairet-Coello G, Risold PY, Griffond B. Orexin/hypocretin neurons: chemical phenotype and possible interactions with melanin-concentrating hormone neurons. Regul Pept. 2002;104(1–3):33–9.

    Article  CAS  PubMed  Google Scholar 

  90. Jego S, Glasgow SD, Herrera CG, Ekstrand M, Reed SJ, Boyce R, Friedman J, Burdakov D, Adamantidis AR. Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat Neurosci. 2013;6(11):1637–43.

    Article  Google Scholar 

  91. Verret L, Goutagny R, Fort P, Cagnon L, Salvert D, Leger L, Boissard R, Salin P, Peyron C, Luppi PH. A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep. BMC Neurosci. 2003;4:19.

    Article  PubMed Central  PubMed  Google Scholar 

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  1. Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, WMRB, Suite 6000, Atlanta, GA, 30322, USA

    Amanda A. H. Freeman PhD

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  1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Aleksandar Videnovic

  2. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    Birgit Högl

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Freeman, A.A.H. (2015). Neurochemistry of the Sleep-Wake Cycle in Parkinson’s Disease. In: Videnovic, A., Högl, B. (eds) Disorders of Sleep and Circadian Rhythms in Parkinson's Disease. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1631-9_2

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