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01-09-2019 | Original Article

The differential impact of acute microglia activation on the excitability of cholinergic neurons in the mouse medial septum

Authors: Orsolya Kékesi, Huazheng Liang, Gerald Münch, John W. Morley, Erika Gyengesi, Yossi Buskila

Published in: Brain Structure and Function | Issue 7/2019

Abstract

The medial septal nucleus is one of the basal forebrain nuclei that projects cholinergic input to the hippocampus and cortex. Two of the hallmarks of Alzheimer’s disease (AD) are a significant loss of cholinergic transmission and neuroinflammation, and it has been suggested that these two hallmarks are causally linked to the medial septum. Therefore, we have investigated the age-related susceptibility of medial septal cholinergic neurons to glial activation, mediated via peripheral administration of lipopolysaccharide (500 μg/kg) into ChAT(BAC)-eGFP mice at different ages (3–22 months). Our results show that during normal aging, cholinergic neurons experience a bi-phasic excitability profile, in which increased excitability at adulthood (ages ranging between 9 and 12 months) decreases in aged animals (> 18 months). Moreover, activation of glia had a differential impact on mice from different age groups, affecting K⁺ conductances in young and adult animals, without affecting aged mice. These findings provide a potential explanation for the increased vulnerability of cholinergic neurons to neuroinflammation with aging as reported previously, thus providing a link to the impact of acute neuroinflammation in AD.

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Title: The differential impact of acute microglia activation on the excitability of cholinergic neurons in the mouse medial septum
Authors: Orsolya Kékesi
Huazheng Liang
Gerald Münch
John W. Morley
Erika Gyengesi
Yossi Buskila
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 7/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-019-01905-w

At a glance: The STEP trials

Springer Medicine

The differential impact of acute microglia activation on the excitability of cholinergic neurons in the mouse medial septum

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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