Deficiency of mesencephalic astrocyte-derived neurotrophic factor affects neurogenesis in mouse brain.

Yongchao Wang, Wen Wen, Hui Li, Hong Xu, Mei Xu, Murong Ma, Jia Luo

Brain research bulletin 2022 Jun 01

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The mechanisms underlying the regulation of neurogenesis in the adult brain remain unclear. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor that has been implicated in various neuropathological processes and endoplasmic reticulum stress. However, the role of MANF in neurogenesis has not been investigated. Using a central nervous system (CNS)-specific Manf knock-out mouse model, we examined the role of MANF in mouse neurogenesis. We demonstrated that MANF deficiency increased BrdU labeling and Ki-67 positive cells in the subgranular zone and subventricular zone. MANF knock-out-induced upregulation of proliferative activity was accompanied by a decrease of cell cycle inhibitors (p15 and p27), an increase of G2/M marker (phospho-histone H3), as well as an increase of neural progenitor markers (Sox2 and NeuroD1) in the brain. In vitro studies using N2A neuroblastoma cells showed that the gain-of-function of MANF inhibited cell cycle progression, whereas the loss-of-function of MANF promoted cell cycle progression. Collectively, our findings indicate MANF deficiency affects cell proliferation and suggest a role of MANF in the neurogenesis of the adult brain. Published by Elsevier Inc.

Citation

Yongchao Wang, Wen Wen, Hui Li, Hong Xu, Mei Xu, Murong Ma, Jia Luo. Deficiency of mesencephalic astrocyte-derived neurotrophic factor affects neurogenesis in mouse brain. Brain research bulletin. 2022 Jun 01;183:49-56