title: 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 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.
authors: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Jennifer
authors: J
authors: Romine
authors: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Xiang
authors: X
authors: Gao
authors: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Xiao-Ming
authors: XM
authors: Xu
authors: Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, Guangdong, China.
authors: Kwok Fai
authors: KF
authors: So
authors: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: chen204@iupui.edu.
authors: Jinhui
authors: J
authors: Chen
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000473:pathology* / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics* / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000473:pathology / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: Aging; Neurogenesis; Proliferation; Stem cell; mTOR