Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease.
Experiments are described in which the benzodiazepine portion of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor and the muscarinic cholinergic receptor were investigated in Parkinson's disease and control brains. Tritiated flunitrazepam and tritiated quinuclidinyl benzilate (QNB) were used to locate and quantify the receptors by autoradiographic and homogenate binding techniques. Densitometric analysis of autoradiographs of the basal ganglia allowed comparison of receptor densities in the post-mortem control and parkinsonian tissue, while homogenate binding experiments gave information concerning receptor affinity and maximum binding capacity. The results indicate that: 1) Binding of flunitrazepam to the benzodiazepine receptor is reduced in the lateral segment of the globus pallidus in Parkinson's disease. This suggest that the GABA-ergic pathway from the putamen to the lateral pallidal segment is overactive in Parkinson's disease. 2) Binding of QNB to the cholinergic receptors of the medial pallidal segment is increased in Parkinson's disease. This finding suggests underactivity of the cholinergic pathway from the pedunculopontine nucleus of the medial pallidal segment. 3) Binding of these ligands in the caudate and putamen of Parkinson's disease is not significantly different from controls. We reviewed the literature concerning the activity of these projections in parkinsonian conditions assessed by different methods and discuss here their implications for the pathogenesis of parkinsonian symptoms.
Griffiths
P D
PD
Department of Cell and Structural Biology, Medical School, University of Manchester, U.K.
Sambrook
M A
MA
Perry
R
R
Crossman
A R
AR
D000368:Aged; D002421:Caudate Nucleus / Q000378:metabolism; D004525:Efferent Pathways / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D005917:Globus Pallidus / Q000378:metabolism*; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism*; D011180:Postmortem Changes; D011699:Putamen / 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; D005445:Flunitrazepam; D011813:Quinuclidinyl Benzilate