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Muscarinic M1 receptors modulate endotoxemia-induced loss of synaptic plasticity

Zivkovic, Aleksandar R. ; Sedlaczek, Oliver ; von Haken, Rebecca ; Schmidt, Karsten ; Brenner, Thorsten ; Weigand, Markus A. ; Bading, Hilmar ; Bengtson, C. Peter ; Hofer, Stefan

In: Acta Neuropathologica Communications, 3 (2015), Nr. 67. pp. 1-12. ISSN 2051-5960

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Download (2MB) | Lizenz: Creative Commons LizenzvertragMuscarinic M1 receptors modulate endotoxemia-induced loss of synaptic plasticity by Zivkovic, Aleksandar R. ; Sedlaczek, Oliver ; von Haken, Rebecca ; Schmidt, Karsten ; Brenner, Thorsten ; Weigand, Markus A. ; Bading, Hilmar ; Bengtson, C. Peter ; Hofer, Stefan underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

Septic encephalopathy is associated with rapid deterioration of cortical functions. Using magnetic resonance imaging (MRI) we detected functional abnormalities in the hippocampal formation of patients with septic delirium. Hippocampal dysfunction was further investigated in an animal model for sepsis using lipopolysaccharide (LPS) injections to induce endotoxemia in rats, followed by electrophysiological recordings in brain slices. Endotoxemia induced a deficit in long term potentiation which was completely reversed by apamin, a blocker of small conductance calcium-activated potassium (SK) channels, and partly restored by treatment with physostigmine (eserine), an acetylcholinesterase inhibitor, or TBPB, a selective M1 muscarinic acetylcholine receptor agonist. These results suggest a novel role for SK channels in the etiology of endotoxemia and explain why boosting cholinergic function restores deficits in synaptic plasticity. Drugs which enhance cholinergic or M1 activity in the brain may prove beneficial in treatment of septic delirium in the intensive care unit.

Item Type: Article
Journal or Publication Title: Acta Neuropathologica Communications
Volume: 3
Number: 67
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 03 Feb 2016 09:56
Date: 2015
ISSN: 2051-5960
Page Range: pp. 1-12
Faculties / Institutes: Service facilities > Interdisziplinäres Zentrum für Neurowissenschaften > IZN Neurobiologie
Medizinische Fakultät Heidelberg > Universitätsklinik für Anaesthesiologie
Medizinische Fakultät Heidelberg > Radiologische Universitätsklinik
Subjects: 570 Life sciences
610 Medical sciences Medicine
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