Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO)

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dc.contributor.authorShi, Yen_AU
dc.contributor.authorCui, Men_AU
dc.contributor.authorOchs, Ken_AU
dc.contributor.authorBrendel, Men_AU
dc.contributor.authorStrübing, FLen_AU
dc.contributor.authorBriel, Nen_AU
dc.contributor.authorEckenweber, Fen_AU
dc.contributor.authorZou, CYen_AU
dc.contributor.authorBanati, RBen_AU
dc.contributor.authorLiu, GJen_AU
dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorRupprecht, Ren_AU
dc.contributor.authorRudolph, Uen_AU
dc.contributor.authorZeilhofer, HUen_AU
dc.contributor.authorRammes, Gen_AU
dc.contributor.authorHerms, Jen_AU
dc.contributor.authorDorostkar, MMen_AU
dc.date.accessioned2022-08-19T06:02:23Zen_AU
dc.date.available2022-08-19T06:02:23Zen_AU
dc.date.issued2022-02-28en_AU
dc.date.statistics2022-08-01en_AU
dc.description.abstractBenzodiazepines 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. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.en_AU
dc.description.sponsorshipThis work was funded by Deutsche Forschungsgemeinschaft grants (FOR 2858 / ID 422181340 to J.H. and M.M.D., ID 420462116 to R.R. and EXC 2145 / ID 390857198 to J.H.).en_AU
dc.identifier.citationShi, Y., Cui, M., Ochs, K., Brendel, M., Strübing, F. L., Briel, N., Eckenweber, F., Zou, C., Banati, R. B., Liu, G. J., Middleton, R. J., Rupprecht, R., Rudolph, U., Zeilhofer, H. U., Rammes, G., Herms, J. & Dorostkar, M. M. (2022). Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO). Nature Neuroscience, 25(3), 317-329. doi:10.1038/s41593-022-01013-9en_AU
dc.identifier.issn1546-1726en_AU
dc.identifier.issue3en_AU
dc.identifier.journaltitleNature Neuroscienceen_AU
dc.identifier.pagination317-329en_AU
dc.identifier.urihttps://doi.org/10.1038/s41593-022-01013-9en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/13587en_AU
dc.identifier.volume25en_AU
dc.language.isoenen_AU
dc.publisherSpringer Natureen_AU
dc.subjectDrugsen_AU
dc.subjectProteinsen_AU
dc.subjectVertebraeen_AU
dc.subjectPlasticityen_AU
dc.subjectMitochondriaen_AU
dc.subjectTherapyen_AU
dc.titleLong-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO)en_AU
dc.typeJournal Articleen_AU
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