| Literature DB >> 27929004 |
Hannah F Iaccarino1,2, Annabelle C Singer3,2,4, Anthony J Martorell1,2, Andrii Rudenko1,2, Fan Gao1,2, Tyler Z Gillingham1,2, Hansruedi Mathys1,2, Jinsoo Seo1,2, Oleg Kritskiy1,2, Fatema Abdurrob1,2, Chinnakkaruppan Adaikkan1,2, Rebecca G Canter1,2, Richard Rueda1,2, Emery N Brown1,2,5,6, Edward S Boyden3,2,4, Li-Huei Tsai1,2,7.
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.Entities:
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Year: 2016 PMID： 27929004 PMCID： PMC5656389 DOI： 10.1038/nature20587
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962