Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation

NEUROBIOLOGY OF AGING

卷:34

Article

Demars, Michael P.¹  Hollands, Carolyn¹  Zhao, Kai Da ( Tommy)¹  Lazarov, Orly¹ 

[1] Univ Illinois, Coll Med, Dept Anat & Cell Biol, Chicago, IL 60612 USA

关键词: Neurogenesis;    Amyloid precursor protein;    Adulthood;    Aging;    Cognition;    Learning and memory;    Alzheimer's disease;   

DOI  :  10.1016/j.neurobiolaging.2013.04.016

来源: Elsevier

【 摘 要 】

Neurogenesis is thought to play a role in cognitive function and hippocampal plasticity. Previous studies suggest that neurogenesis declines with aging. However, the onset and mechanism of declined neurogenesis are not fully elucidated. Here we show that the major decline in neurogenesis takes place during adulthood, before aging. Decline in neurogenesis takes place in the subgranular layer of the dentate gyrus and in the subventricular zone, and is primarily due to a reduced number of fast-proliferating neural progenitor cells. Importantly, this decline can be rescued by intraventricular injection of recombinant soluble amyloid precursor protein (sAPP alpha), which regulates neural progenitor cell proliferation in the adult brain. The counterpart, sAPP beta, a product of the amyloidogenic cleavage pathway of amyloid precursor protein, fails to exhibit a proliferative effect in vitro and in vivo, in equimolar concentrations to sAPP alpha. These observations suggest that adulthood is an appropriate time window for an intervention that upregulates neurogenesis, such as enhancement of sAPP alpha levels, for the prevention of declining brain plasticity and cognitive function. (c) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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