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Neurotransmitter Receptor Imbalances in Motor Cortex and Basal Ganglia in Hepatic EncephalopathyPalomero-Gallagher N.1,2 · Bidmon H.-J.3 · Cremer M.1 · Schleicher A.3 · Kircheis G.4 · Reifenberger G.5 · Kostopoulos G.6 · Häussinger D.4 · Zilles K.1,2,3,7
1Institute of Neurosciences and Medicine (INM-2), Research Center Jülich,2JARA - Translational Brain Medicine,3C.&O. Vogt Institute of Brain Research, Heinrich-Heine-University, Düsseldorf,4Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Düsseldorf,5Department of Neuropathology, Heinrich-Heine-University, Düsseldorf,6Medical School, University of Patras, Patras,7Brain Imaging Center West, Research Center Jülich, Jülich Corresponding Author
Institute of Neurosciences and Medicine (INM-2)
Research Center Jülich, 52425 Jülich (Germany)
Tel. +49-2461 614790, Fax: +49-2461 612820
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.
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