Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model

被引：691

作者：

Choi, Se Hoon ^{[1
]}

Bylykbashi, Enjana ^{[1
]}

Chatila, Zena K. ^{[1
,7
]}

Lee, Star W. ^{[2
,8
]}

Pulli, Benjamin ^{[3
]}

Clemenson, Gregory D. ^{[2
,9
]}

Kim, Eunhee ^{[1
]}

Rompala, Alexander ^{[1
]}

Oram, Mary K. ^{[1
]}

Asselin, Caroline ^{[1
]}

Aronson, Jenna ^{[1
,10
]}

Zhang, Can ^{[1
]}

Miller, Sean J. ^{[1
,11
]}

Lesinski, Andrea ^{[1
,12
]}

Chen, John W. ^{[3
]}

Kim, Doo Yeon ^{[1
]}

van Praag, Henriette ^{[4
,5
]}

Spiegelman, Bruce M. ^{[6
]}

Gage, Fred H. ^{[2
]}

Tanzi, Rudolph E. ^{[1
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Genet & Aging Res Unit, Dept Neurol, Charlestown, MA 02129 USA

[2] Salk Inst Biol Studies, Lab Genet, La Jolla, CA 92037 USA

[3] Massachusetts Gen Hosp, Inst Innovat Imaging, Dept Radiol, Boston, MA 02114 USA

[4] Florida Atlantic Univ, Dept Biomed Sci, Charles E Schmidt Coll Med, Jupiter, FL 33458 USA

[5] Florida Atlantic Univ, Brain Inst, Jupiter, FL 33458 USA

[6] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[7] Columbia Univ, Dept Neurosci, New York, NY 10036 USA

[8] Univ Calif Riverside, Dept Evolut Ecol & Organismal Biol, Riverside, CA 92521 USA

[9] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA

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

[11] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA

[12] Univ Rhode Isl, Cell & Mol Biol, Kingston, RI 02881 USA

来源：

SCIENCE | 2018年 / 361卷 / 6406期

关键词：

PROGENITOR-CELL PROLIFERATION; HIPPOCAMPAL NEUROGENESIS; TRANSGENIC MICE; DENTATE GYRUS; ENVIRONMENTAL ENRICHMENT; BRAIN HEALTH; AGED MICE; DISEASE; NEURODEGENERATION; IL-6;

D O I：

10.1126/science.aan8821

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's disease (AD) pathology. We found that exercise provided cognitive benefit to 5xFAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain-derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor exercise, in the absence of increased AHN, ameliorated cognition. We successfully mimicked the beneficial effects of exercise on AD mice by genetically and pharmacologically inducing AHN in combination with elevating BDNF levels. Suppressing AHN later led to worsened cognitive performance and loss of preexisting dentate neurons. Thus, pharmacological mimetics of exercise, enhancing AHN and elevating BDNF levels, may improve cognition in AD. Furthermore, applied at early stages of AD, these mimetics may protect against subsequent neuronal cell death.

引用

页码：991 / +

页数：16

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