Gamma frequency entrainment attenuates amyloid load and modifies microglia
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Le résumé fourni par la source
Abstract Changes in gamma oscillations (20–50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer’s disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)1–40 and Aβ 1–42 isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ1–40 and Aβ1–42 levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer’s-disease-associated pathology.
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Où se fait cette recherche
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Massachusetts Institute of Technology Department of Brain and Cognitive Sciences pays non établi dans la noticeUniversité ou école supérieure
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McGovern Institute for Brain Research pays non établi dans la noticeStructure de recherche
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Institute of Cognitive and Brain Sciences pays non établi dans la noticeUniversité ou école supérieure
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MIT Media Lab Departments of Biological Engineering and Brain and Cognitive Sciences pays non établi dans la noticeStructure de recherche
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Broad Institute pays non établi dans la noticeOrganisation à but non lucratif
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Picower Institute for Learning and Memory pays non établi dans la noticeStructure de recherche
Department of Brain and Cognitive Sciences — Massachusetts Institute of Technology, McGovern Institute for Brain Research et Institute of Cognitive and Brain Sciences, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.