Restoring Carboxypeptidase E Rescues BDNF Maturation and Neurogenesis in Aged Brains
Restoring Carboxypeptidase E Rescues BDNF Maturation and Neurogenesis in Aged Brains
复制标题
DOI：
10.1093/lifemedi/lnad015
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Tie-Shan Tang
中科院分区：
文献类型：
--
作者：
Hongmei Liu;Dongfang Jiang;Fuwen Yao;Tingting Li;Bo Zhou;Song Zhao;Keyan Yang;Haiping Feng;Jiaqi Shen;Jinglan Tang;Sijia Wang;Yu-Xin Zhang;Yun Wang;Qian Li;Yongliang Zhao;Caixia Guo;Tie-Shan Tang
Abstract. Adult neurogenesis declines with age due to the less functional neural stem cells (NSCs) and niches, but the underlying molecular bases for this impaired condition remain unclear. Here we analyzed >55,000 single-cell transcriptomes from two discrete neurogenic niches across the mouse lifespan, and identified new features and populations in NSCs, new markers and neurogenic regional-specific alternations during aging. Intercellular communication analysis revealed defects in brain-derived neurotrophic factor (BDNF)-TrkB signaling cascade in old NSCs. Carboxypeptidase E (CPE) was found to be highly enriched in NSCs, and played a crucial role in mature/pro-BDNF balance and adult neurogenesis. Diminishment of CPE with aging resulted in impaired generation of BDNF, thus limiting the neurogenesis in old neurogenic niches. Restoring CPE expression markedly rescued the adult neurogenesis by increasing the production of mature BDNF, offering an attractive therapeutic strategy for the treatment of certain disorders in regions associated with constitutive neurogenesis.
