Lupo Giuseppe, Gioia Roberta, Nisi Paola Serena, Biagioni Stefano, Cacci Emanuele
Department of Chemistry, Sapienza University of Rome, Rome, Italy.
Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Rome, Italy.
J Exp Neurosci. 2019 Feb 19;13:1179069519829040. doi: 10.1177/1179069519829040. eCollection 2019.
In the adult rodent brain, the continuous production of new neurons by neural stem/progenitor cells (NSPCs) residing in specialized neurogenic niches and their subsequent integration into pre-existing cerebral circuitries supports odour discrimination, spatial learning, and contextual memory capabilities. Aging is recognized as the most potent negative regulator of adult neurogenesis. The neurogenic process markedly declines in the aged brain, due to the reduction of the NSPC pool and the functional impairment of the remaining NSPCs. This decline has been linked to the progressive cognitive deficits of elderly individuals and it may also be involved in the onset/progression of neurological disorders. Since the human lifespan has been dramatically extended, the incidence of age-associated neuropsychiatric conditions in the human population has increased. This has prompted efforts to shed light on the mechanisms underpinning the age-related decline of adult neurogenesis, whose knowledge may foster therapeutic approaches to prevent or delay cognitive alterations in elderly patients. In this review, we summarize recent progress in elucidating the molecular causes of neurogenic aging in the most abundant NSPC niche of the adult mouse brain: the subventricular zone (SVZ). We discuss the age-associated changes occurring both in the intrinsic NSPC molecular networks and in the extrinsic signalling pathways acting in the complex environment of the SVZ niche, and how all these changes may steer young NSPCs towards an aged phenotype.
在成年啮齿动物大脑中，位于特殊神经发生微环境中的神经干细胞/祖细胞（NSPCs）持续产生新的神经元，随后这些新神经元整合到预先存在的脑回路中，这有助于气味辨别、空间学习和情境记忆能力。衰老被认为是成年神经发生最有力的负调节因子。由于NSPC库的减少和剩余NSPCs的功能受损，神经发生过程在老年大脑中明显下降。这种下降与老年人逐渐出现的认知缺陷有关，也可能参与神经疾病的发生/发展。由于人类寿命显著延长，人群中与年龄相关的神经精神疾病的发病率增加。这促使人们努力阐明成年神经发生与年龄相关下降的机制，了解这些机制可能有助于开发预防或延缓老年患者认知改变的治疗方法。在这篇综述中，我们总结了在阐明成年小鼠大脑中最丰富的NSPC微环境——脑室下区（SVZ）中神经发生衰老的分子原因方面的最新进展。我们讨论了在SVZ微环境复杂环境中，内在NSPC分子网络和外在信号通路中发生的与年龄相关的变化，以及所有这些变化如何使年轻的NSPCs转变为衰老表型。
