Alterations of neurotransmitter receptors and neurotransmitter transporters in progressive supranuclear palsy.
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 interneurons, 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.
Landwehrmeyer
B
B
Department of Pathology, University of Basel, Switzerland.
Palacios
J M
JM
D000368:Aged; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000235:genetics; D011963:Receptors, GABA-A / Q000032:analysis; D011976:Receptors, Muscarinic / Q000032:analysis; D018028:Receptors, Neurotensin / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000032:analysis*; D013373:Substance P / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism*
D002352:Carrier Proteins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; D013373:Substance P; D004298:Dopamine