The proliferation of amplifying neural progenitor cells is impaired in the aging brain and restored by the mTOR pathway activation

Abstract A decrease in neurogenesis in the aged brain has been correlated with cognitive decline. The molecular signaling that regulates age-related decline in neurogenesis is still not fully understood. We found that different subtypes of neural stem cells (NSCs) in the hippocampus were differentia...

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Bibliographic Details
Published in:Neurobiology of aging 2015-04, Vol.36 (4), p.1716-1726
Main Authors: Romine, Jennifer, Gao, Xiang, Xu, Xiao-Ming, So, Kwok Fai, Chen, Jinhui
Format: Article
Language:English
Subjects:
Aging
Aging - pathology
Aging - physiology
Animals
Brain - cytology
Brain - pathology
Brain - physiology
Cell Proliferation - genetics
Cell Proliferation - physiology
Hippocampus - cytology
Hippocampus - pathology
Hippocampus - physiology
Internal Medicine
Male
Mice, Inbred C57BL
mTOR
Neural Stem Cells - cytology
Neurogenesis
Neurogenesis - genetics
Neurogenesis - physiology
Neurology
Proliferation
Signal Transduction - genetics
Signal Transduction - physiology
Stem cell
TOR Serine-Threonine Kinases - physiology
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Summary:Abstract A decrease in neurogenesis in the aged brain has been correlated with cognitive decline. The molecular signaling that regulates age-related decline in neurogenesis is still not fully understood. We found that different subtypes of neural stem cells (NSCs) in the hippocampus were differentially impaired by aging. The quiescent NSCs decreased slowly, although the active NSCs exhibited a sharp and dramatic decline from the ages of 6–9 months and became more quiescent at an early stage during the aging process. The activity of the mammalian target of rapamycin (mTOR) signal pathway is compromised in the NSCs of the aged brain. Activating the mTOR signaling pathway increased NSC proliferation and promoted neurogenesis in aged mice. In contrast, inhibiting the mTOR signaling pathway decreased NSCs proliferation. These results indicate that an age-associated decline in neurogenesis is mainly because of the reduction in proliferation of active NSCs, at least partially because of the compromise in the mTOR signaling activity. Stimulating the mTOR signaling revitalizes the NSCs, restores their proliferation, and enhances neurogenesis in the hippocampus of the aged brain.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2015.01.003