Gamma frequency entrainment attenuates amyloid load and modifies microglia

被引：859

作者：

Iaccarino, Hannah F. ^{[1
,3
]}

Singer, Annabelle C. ^{[2
,3
,4
,5
,9
]}

Martorell, Anthony J. ^{[1
,3
]}

Rudenko, Andrii ^{[1
,3
,10
]}

Gao, Fan ^{[1
,3
]}

Gillingham, Tyler Z. ^{[1
,3
]}

Mathys, Hansruedi ^{[1
,3
]}

Seo, Jinsoo ^{[1
,3
]}

Kritskiy, Oleg ^{[1
,3
]}

Abdurrob, Fatema ^{[1
,3
]}

Adaikkan, Chinnakkaruppan ^{[1
,3
]}

Canter, Rebecca G. ^{[1
,3
]}

Rueda, Richard ^{[1
,3
]}

Brown, Emery N. ^{[1
,3
,6
,7
]}

Boyden, Edward S. ^{[2
,3
,4
,5
]}

Tsai, Li-Huei ^{[1
,3
,8
]}

机构：

[1] MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[2] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[3] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA

[4] MIT, Dept Biol Engn, MIT Media Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[5] MIT, Dept Brain & Cognit Sci, MIT Media Lab, E25-618, Cambridge, MA 02139 USA

[6] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[7] Massachusetts Gen Hosp, Boston, MA 02114 USA

[8] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA

[9] Emory Univ, Georgia Inst Technol, Coulter Dept Biomed Engn, Atlanta, GA 30332 USA

[10] CUNY, Dept Biol, New York, NY 10031 USA

来源：

NATURE | 2016年 / 540卷 / 7632期

基金：

美国国家卫生研究院;

关键词：

HIPPOCAMPAL PLACE CELLS; ALZHEIMERS-DISEASE; NEURONAL-ACTIVITY; BETA DEPOSITION; NEURAL CIRCUITS; VISUAL-CORTEX; AWAKE STATE; MOUSE MODEL; OSCILLATIONS; ACTIVATION;

D O I：

10.1038/nature20587

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-beta (A beta)(1-40) and A beta(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 A beta. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced A beta(1-40) and A beta(1-42) 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.

引用

页码：230 / +

页数：22

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