ALTERATIONS OF NEUROTRANSMITTER RECEPTORS AND NEUROTRANSMITTER TRANSPORTERS IN PROGRESSIVE SUPRANUCLEAR PALSY

Neurotransmitter receptors and neurotransmitter transporters were stud ied postmortem in the brains of 9 PSP patients by receptor autoradiogr aphy. Densities of dopamine uptake sites and neurotensin receptors wer e significantly reduced in striatum and substantia nigra consistent wi th a localization of these binding sites on degenerating dopaminergic nigrostriatal projection neurons. The densities of dopamine D-1 recept ors were unchanged. Dopamine D-2 receptors were unaltered when labeled by [I-125]-Iodosulpride or [H-3]-CV 205 502, but appeared to be signi ficantly reduced when labeled by [H-3]-spiperone. Levels of D-2 mRNA w ere comparable to control levels, suggesting that only subtypes of Dop amine D-2-like receptors may be affected in PSP. Serotonin (5-HT) upta ke sites and 5-HT receptors were not altered. The density of muscarini c receptors was reduced in striatum, possibly related to a degeneratio n of cholinergic striatal interneurons, but increased in internal glob us pallidus. GABA(A)/BZ receptor binding sites were significantly redu ced in both segments of globus pallidus, probably as a consequence of severe degeneration of intrinsic pallidal neurons in PSP. Binding of s ubstance P in striatum tended to be decreased but failed to reach stat istical significance. Compared to Parkinson's disease, the densities o f more neurotransmitter receptors were altered in PSP. With the except ion of increased muscarinic receptor binding sites in medial globus pa llidus, the alterations seen in PSP seem to reflect cell loss rather t han functional changes.