Alterations of neurotransmitter receptors and neurotransmitter transporters in progressive supranuclear palsy

  • B. Landwehrmeyer
  • J. M. Palacios
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 42)


Neurotransmitter receptors and neurotransmitter transporters were studied postmortem in the brains of 9 PSP patients by receptor autoradiography. Densities of dopamine uptake sites and neurotensin receptors were significantly reduced in striatum and substantia nigra consistent with a localization of these binding sites on degenerating dopaminergic nigrostriatal projection neurons. The densities of dopamine D1 receptors were unchanged. Dopamine D2 receptors were unaltered when labeled by [125I]-Iodosulpride or [3H]-CV 205 502, but appeared to be significantly reduced when labeled by [3H]-spiperone. Levels of D2 mRNA were comparable to control levels, suggesting that only subtypes of Dopamine D2-like receptors may be affected in PSP. Serotonin (5-HT) uptake sites and 5-HT receptors were not altered. The density of muscarinic receptors was reduced in striatum, possibly related to a degeneration of cholinergic striatal inter-neurons, but increased in internal globus pallidus. GABAA/BZ receptor binding sites were significantly reduced in both segments of globus pallidus, probably as a consequence of severe degeneration of intrinsic pallidal neurons in PSP. Binding of substance P in striatum tended to be decreased but failed to reach statistical significance. Compared to Parkinson’s disease, the densities of more neurotransmitter receptors were altered in PSP. With the exception of increased muscarinic receptor binding sites in medial globus pallidus, the alterations seen in PSP seem to reflect cell loss rather than functional changes.


Muscarinic Receptor Globus Pallidus Progressive Supranuclear Palsy Neurotransmitter Receptor Internal Globus Pallidus 
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  1. Agid Y, Javoy-Agid F, Ruberg M, Pillon B, Dubois B, Duyckaerts C., Hauw J-J, Baron J-C, Scatton B (1986) Progressive supranuclear palsy: anatomoclinical and biochemical considerations. In: Yahr MD, Bergman KJ (eds) Advances in neurology, vol 45. Raven Press, New York.Google Scholar
  2. Behrman S, Carroll JD, Janota I, Matthews WB (1969) Progressive supranuclear palsy. Brain 92: 663–678.PubMedCrossRefGoogle Scholar
  3. Bokobza B, Ruberg M, Scatton B, Javoy-Agid F, Agid Y (1984) [3H]-spiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 99: 167–175.PubMedCrossRefGoogle Scholar
  4. Braak H, Jellinger K, Braak E, Bohl J (1992) Allocortical neurofibrillary changes in progressive supranuclear palsy. Acta Neuropathol 84: 478–483.PubMedCrossRefGoogle Scholar
  5. Charuchinda C, Supavilai P, Karobath M, Palacios JM (1987) Dopamine D2 receptors in the rat brain: autoradiographic visualization using a high-affinity selective agonist ligand. J Neurosci 7: 1352–1360.PubMedGoogle Scholar
  6. Chinaglia G, Probst A, Palacios JM (1990) Neurotensin receptors in Parkinson’s disease and progressive supranuclear palsy: an autoradiographic study in basal ganglia. Neuroscience 39: 351–360.PubMedCrossRefGoogle Scholar
  7. Chinaglia G, Alvarez FJ, Probst A, Palacios JM (1992) Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson’s disease and progressive supranuclear palsy: a quantitative autoradiographic study using [3H]-mazindol. Neuroscience 49: 317–327.PubMedCrossRefGoogle Scholar
  8. Chinaglia G, Landwehrmeyer B, Probst A, Palacios JM (1993) Serotoninergic terminals are differentially affected in Parkinson’s disease and progressive supranuclear palsy: an autoradiographic study with [3H]-citalopram. Neuroscience 54: 691–699.PubMedCrossRefGoogle Scholar
  9. Cortés R, Probst A, Palacios JM (1987) Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: forebrain. Neuroscience 20: 65–107.PubMedCrossRefGoogle Scholar
  10. Cortés R, Camps M, Gueye B, Probst A, Palacios JM (1989) Dopamine receptors in human brain: autoradiographic distribution of D1 and D2 sites in Parkinson syndrome of different etiology. Brain Res 483: 30–38.PubMedCrossRefGoogle Scholar
  11. D’Amato RJ, Largent BL, Snowman AM, Snyder SH (1987) Selective labeling of serotonin uptake sites in rat brain by [3H]citalopram contrasted to labeling of multiple sites by [3H]imipramine. J Pharmacol Exp Ther 242: 364–371.Google Scholar
  12. Dietl MM, Sanchez M, Probst A, Palacios JM (1989) Substance P receptors in the human spinal cord: decrease in amyotrophic lateral sclerosis. Brain Res 483: 39–49.PubMedCrossRefGoogle Scholar
  13. Gerfen CR (1991) Substance P (neurokinin-1) receptor mRNA is selectively expressed in cholinergic neurons in the striatum and basal forebrain. Brain Res 556: 165–170.PubMedCrossRefGoogle Scholar
  14. Golbe LI, Davies PH (1988) Progressive supranuclear palsy. In: Jankovic J, Tolosa E (eds) Parkinson’s disease and movement disorders. Urban & Schwarzenberg, Baltimore, pp 121–130.Google Scholar
  15. Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC, Civelli O (1989) Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc Natl Acad Sci USA 86: 9762–9766.PubMedCrossRefGoogle Scholar
  16. Hauw J-J, Verny M, Delaère P, Cervera P, He Y, Duyckaerts C (1990) Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy: basic differences with Alzheimer’s disease. Neurosci Lett 119: 182–186.PubMedCrossRefGoogle Scholar
  17. 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: 5976–5980.PubMedCrossRefGoogle Scholar
  18. Hirsch EC, Graybiel AM, Hersh LB, Duyckaerts C, Agid Y (1989) Striosomes and extrastriosomal matrix contain different amounts of immunoreactive choline acetyl-transferase in the human striatum. Neurosci Lett 96: 145–150.PubMedCrossRefGoogle Scholar
  19. Hof PR, Delacourte A, Bouras C (1992) Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases. Acta Neuropathol 84: 45–51.PubMedCrossRefGoogle Scholar
  20. Ishino H, Ikeda H, Otsuki S (1975) Contribution to clinical pathology of progressive supranuclear palsy (subcortical argyrophilic dystrophy). On the distribution of neurofibrillary tangles in the basal ganglia and brain-stem and its clinical significance. J Neurol Sci 24: 471–481.PubMedCrossRefGoogle Scholar
  21. Javitch JA, Strittmatter SM, Snyder SH (1985) Differential visualization of dopamine and norepinephrine uptake sites in rat brain using [3H]mazindol autoradiography. J Neurosci 5: 1513–1521.PubMedGoogle Scholar
  22. Jellinger K, Riederer P, Tomonaga M (1980) Progressive supranuclear palsy: clinico-pathological and biochemical studies. J Neural Transm [Suppl] 16: 111–128.Google Scholar
  23. Jellinger K (1988) The pedunculopontine nucleus in Parkinson’s disease, progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 51: 540–543.PubMedCrossRefGoogle Scholar
  24. Kish SJ, Chang LJ, Mirchandani L, Shannak K, Hornykiewicz O (1985) Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers. Ann Neurol 18: 530–536.PubMedCrossRefGoogle Scholar
  25. Landwehrmeyer B, Mengod G, Palacios JM (1993) Differential visualization of dopamine D2 and D3 receptor sites in rat brain. A comparative study using in situ hybridization histochemistry and ligand binding autoradiography. Eur J Neurosci 5: 145–153.PubMedCrossRefGoogle Scholar
  26. Maher ER, Lees AJ (1986) The clinical features and natural history of the Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 36: 1005–1008.PubMedCrossRefGoogle Scholar
  27. Martres M-P, Bouthenet M-L, Sales N, Sokoloff P, Schwartz J-C (1985) Widespread distribution of brain dopamine receptors evidenced with [125I]Iodosulpride, a highly selective ligand. Science 228: 752–755.PubMedCrossRefGoogle Scholar
  28. Mengod G, Vilaró MT, Landwehrmeyer GB, Martinez-Mir MI, Niznik HB, Sunahara RK, Seeman P, O’Dowd BF, Probst A, Palacios JM (1992) Visualization of dopamine D1, D2 and D3 receptor mRNAs in human and rat brain. Neurochem Int 20: 33S–43S.PubMedCrossRefGoogle Scholar
  29. Newman GC (1985) Treatment of progressive supranuclear palsy with tricyclic antidepressants. Neurology 35: 1189–1193.PubMedCrossRefGoogle Scholar
  30. Oberlander C, Blaquière B, Pujol J-F (1986) Distinct functions for dopamine and serotonin in locomotor behavior: evidence using the 5-HT1 agonist RU 24969 in globus pallidus-lesioned rats. Neurosci Lett 67: 113–118.PubMedCrossRefGoogle Scholar
  31. Oyanagi K, Takahashi H, Wakabayashi K, Ikuta F (1991) Large neurons in the neostriatum in Alzheimer’s disease and progressive supranuclear palsy: a topographic, histologic and ultrastructural investigation. Brain Res 544: 221–226.PubMedCrossRefGoogle Scholar
  32. Palacios JM, Niehoff DL, Kuhar MJ (1981) [3H]spiperone binding sites in brain: autoradiographic localization of multiple receptors. Brain Res 213: 277–289.PubMedCrossRefGoogle Scholar
  33. Palacios JM, Landwehrmeyer B, Mengod G (1993) Brain dopamine receptors: characterization, distribution and alteration in disease. In: Jankovic J, Tolosa E (eds) Parkinson’s disease and movement disorders, 2nd edn. Williams & Wilkins, Baltimore, pp 35–54.Google Scholar
  34. Pierot L, Desnos C, Blin J, Raisman R, Scherman D, Javoy-Agid F, Ruberg M, Agid Y (1988) D1 and D2-type dopamine receptors in patients with Parkinson’s disease and progressive supranuclear palsy. J Neurol Sci 86: 291–306.PubMedCrossRefGoogle Scholar
  35. Probst A, Langui D, Lautenschlager C, Ulrich J, Brion JP, Anderton BH (1988) Progressive supranuclear palsy: extensive neuropil threads in addition to neurofibrillary tangles. Very similar antigenicity of subcortical neuronal pathology in progressive supranuclear palsy and Alzheimer’s disease. Acta Neuropathol 77: 61–68.PubMedCrossRefGoogle Scholar
  36. Ruberg M, Javoy-Agid F, Hirsch E, Scatton B, Heureux RL, Hauw J-J, Duyckaerts Ch, Gray F, Morel-Maroger A, Rascol A, Serdaru M, Agid Y (1985) Dopaminergic and cholinergic lesions in progressive supranuclear palsy. Ann Neurol 18: 523–529.PubMedCrossRefGoogle Scholar
  37. Steele JC, Richardson JC, Olzewski J (1964) Progressive supranuclear palsy. Arch Neurol 10: 333–359.PubMedCrossRefGoogle Scholar
  38. Steele JC (1972) Progressive supranuclear palsy. Brain 95: 693–704.PubMedGoogle Scholar
  39. Tagliavini F, Pilleri G, Gemignani F, Lechi A (1983) Neuronal loss in the basal nucleus of Meynert in progressive supranuclear palsy. Acta Neuropathol 61: 157–160.PubMedCrossRefGoogle Scholar
  40. Uhl GR, Snyder SH (1977) Neurotensin receptor binding, regional and subcellular distributions favour transmitter role. Eur J Pharmacol 41: 89–91.PubMedCrossRefGoogle Scholar
  41. Vilaró MT, Wiederhold KH, Palacios JM, Mengod G (1991) Muscarinic M2 receptor mRNA expression and receptor binding in cholinergic and noncholinergic cells in the rat brain: a correlative study using in situ hybridization and receptor autor-adiography. Neuroscience 47: 367–393.CrossRefGoogle Scholar
  42. Wamsley JK, Zarbin MA, Birdsall JM, Kuhar MJ (1980) Muscarinic cholinergic receptors: autoradiographic localization of high and low affinity agonist binding sites. Brain Res 200: 1–12.PubMedCrossRefGoogle Scholar
  43. Zezula J, Cortés R, Probst A, Palacios JM (1988) Benzodiazepine receptor sites in the human brain: autoradiographic mapping. Neuroscience 25: 771–795.PubMedCrossRefGoogle Scholar
  44. Zweig RM, Whitehouse PJ, Casanova MF, Walker LC, Jankel WR, Price DL (1987) Loss of pedunculopontine neurons in progressive supranuclear palsy. Ann Neurol 22: 18–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1994

Authors and Affiliations

  • B. Landwehrmeyer
    • 1
  • J. M. Palacios
    • 2
    • 3
  1. 1.Department of Pathology, Division of NeuropathologyUniversity of BaselBaselSwitzerland
  2. 2.Laboratorios AlmirallS. A., Research InstituteBarcelonaSpain
  3. 3.Laboratorios AlmirallBarcelonaSpain

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