GABAA receptor but not muscarinic receptor density was decreased in the brain of patients with Parkinson's disease.
The activity of glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) as presynaptic markers of gamma-aminobutyric acid (GABA)- and acetylcholine (ACh)-containing neurons, and the binding of [3H]muscimol and [3H]quinuclidinyl benzilate ([3H]QNB) as postsynaptic ones were measured in autopsied samples of the caudate nucleus, putamen, pallidum, substantia nigra and the cerebral cortex from L-dopa-treated patients with Stage V (terminally bedridden) patients with Parkinson's Disease (PD). In PD, GAD activities were significantly reduced in the caudate nucleus and substantia nigra relative to normal controls, but were normal when the values from protracted terminal illness (PTI) cases were used as the controls. ChAT activities were reduced in all regions studied. These reductions in GAD and ChAT activities were not accompanied by a concomitant increase in the density of GABAA or muscarinic receptors. GABAA receptor densities were significantly decreased in both the cortical and subcortical brain regions, while muscarinic receptor densities remained unchanged. We suggest that the decreased density of GABAA receptor in PD brains reflects degeneration of neurons on which the receptor is localized, i.e., degeneration of ascending monoaminergic neurons including nigral dopamine (DA) neurons.
Nishino
N
N
Department of Pharmacology, Kobe University School of Medicine, Japan.
Fujiwara
H
H
Noguchi-Kuno
S A
SA
Tanaka
C
C
D000368:Aged; D001921:Brain / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009118:Muscimol / Q000378:metabolism; D009410:Nerve Degeneration; D010300:Parkinson Disease / Q000378:metabolism*; D010890:Pirenzepine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D009118:Muscimol; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D004298:Dopamine