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- Title
Neurotransmitter Receptor Imbalances in Motor Cortex and Basal Ganglia in Hepatic Encephalopathy.
- Authors
Palomero-Gallagher, Nicola; Bidmon, Hans-Jürgen; Cremer, Markus; Schleicher, Axel; Kircheis, Gerald; Reifenberger, Guido; Kostopoulos, George; Häussinger, Dieter; Zilles, Karl
- Abstract
Hepatic encephalopathy (HE) in chronic liver disease is characterized by neuropsychiatric and motor disturbances and associated with a net increase of inhibitory neurotransmission. Though many studies, mostly carried out in animal models, have linked dysfunctions of single neurotransmitter systems with the pathogenesis of HE, reports concerning neurotransmitter receptor alterations are controversial. Little is known about the situation in humans. We carried out a multireceptor assessment of HE-associated changes in neurotransmitter receptor densities and affinities in human post-mortem brain samples. Dissociation constants and densities of different binding sites for glutamate, GABA, acetylcholine, norepinephrine, serotonin, dopamine and adenosine were determined by in vitro binding assays and quantitative receptor autoradiography in the motor cortex and putamen of HE and control brains. HE cases do not build a homogeneous group, but differ concerning direction and intensity of binding site density divergences from control values. The acetylcholine M2 binding site dissociation constant was significantly higher in HE brains. Nicotinic acetylcholine and adenosine type 1 and 2A densities were significantly down-regulated in the putamen of HE brains. Our data suggest that neurotransmitter alterations are probably not the primary key factor responsible for the neuropsychiatric and motor disturbances associated with HE. Copyright © 2009 S. Karger AG, Basel
- Subjects
BRAIN; TISSUES; LIVER diseases; MOTOR cortex; ADENOSINES; NEUROTRANSMITTER receptors
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2009, Vol 24, Issue 3/4, p291
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000233254