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Science. 2018 Sep 7;361(6406). pii: eaan8821. doi: 10.1126/science.aan8821.

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

Author information

1
Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
2
Laboratoy of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3
Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA.
4
Department of Biomedical Science, Charles E. Schmidt College of Medicine, and Brain Institute, Florida Atlantic University, Jupiter, FL 33458, USA.
5
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
6
Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. tanzi@helix.mgh.harvard.edu.

Abstract

Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's disease (AD) pathology. We found that exercise provided cognitive benefit to 5×FAD 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.

PMID:
30190379
PMCID:
PMC6149542
[Available on 2019-03-07]
DOI:
10.1126/science.aan8821

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