Abstract
ABSTRACTNeuropathological aging is associated with memory impairment and cognitive decline, and affects several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain homeostatic mechanisms regulate neurogenesis in the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells, and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population.Our work is aimed to discover targeting molecules to be used in the design of pharmacological agents to prevent the neurological effects of pathological aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of pathological aging. Thus, we show that in six-month-old SAMP8 mice, episodic and spatial memory are impaired, concomitantly the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a TGF-alpha targeting molecule, prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGF-alpha in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that targeting the release of TGF-alpha may be the basis of pharmacological drugs to counteract the neurological effects of pathological aging.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献