| Literature DB >> 35228700 |
Jochen Herms1,2,3, Mario M Dorostkar4,5, Yuan Shi6,7,8,9, Mochen Cui6,7,9, Katharina Ochs6,7, Matthias Brendel10, Felix L Strübing6,7, Nils Briel6,7,9, Florian Eckenweber10, Chengyu Zou6,7,11, Richard B Banati12,13, Guo-Jun Liu12,13, Ryan J Middleton12, Rainer Rupprecht14, Uwe Rudolph15, Hanns Ulrich Zeilhofer16,17, Gerhard Rammes18.
Abstract
Benzodiazepines are widely administered drugs to treat anxiety and insomnia. In addition to tolerance development and abuse liability, their chronic use may cause cognitive impairment and increase the risk for dementia. However, the mechanism by which benzodiazepines might contribute to persistent cognitive decline remains unknown. Here we report that diazepam, a widely prescribed benzodiazepine, impairs the structural plasticity of dendritic spines, causing cognitive impairment in mice. Diazepam induces these deficits via the mitochondrial 18 kDa translocator protein (TSPO), rather than classical γ-aminobutyric acid type A receptors, which alters microglial morphology, and phagocytosis of synaptic material. Collectively, our findings demonstrate a mechanism by which TSPO ligands alter synaptic plasticity and, as a consequence, cause cognitive impairment.Entities:
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Year: 2022 PMID： 35228700 DOI： 10.1038/s41593-022-01013-9
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 28.771