期刊
CELLS
卷 11, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/cells11172661
关键词
hippocampal adult neurogenesis; neural stem and progenitor cells; epigenetics; maternal HFD
类别
资金
- Italian Ministry of University and Research [SIR 2014 RBSI14ZV59]
- Ministero della Salute-Ricerca Corrente 2022 Fondazione Policlinico Universitario A. Gemelli IRCCS
This study reveals that maternal high fat diet has multigenerational effects on hippocampal adult neurogenesis. The altered expression of genes regulating stem cell proliferation and neurodifferentiation in neural stem and progenitor cells (NSPCs) contribute to the depletion of neurogenic niche caused by maternal high fat diet. Furthermore, an epigenetic derangement induced by ancestor high fat diet is associated with the depletion of neurogenic niche.
Early-life metabolic stress has been demonstrated to affect brain development, persistently influence brain plasticity and to exert multigenerational effects on cognitive functions. However, the impact of an ancestor's diet on the adult neurogenesis of their descendants has not yet been investigated. Here, we studied the effects of maternal high fat diet (HFD) on hippocampal adult neurogenesis and the proliferation of neural stem and progenitor cells (NSPCs) derived from the hippocampus of both the second and the third generations of progeny (F2(HFD) and F3(HFD)). Maternal HFD caused a multigenerational depletion of neurogenic niche in F2(HFD) and F3(HFD) mice. Moreover, NSPCs derived from HFD descendants showed altered expression of genes regulating stem cell proliferation and neurodifferentiation (i.e., Hes1, NeuroD1, Bdnf). Finally, ancestor HFD-related hyper-activation of both STAT3 and STAT5 induced enhancement of their binding on the regulatory sequences of Gfap gene and an epigenetic switch from permissive to repressive chromatin on the promoter of the NeuroD1 gene. Collectively, our data indicate that maternal HFD multigenerationally affects hippocampal adult neurogenesis via an epigenetic derangement of pro-neurogenic gene expression in NSPCs.
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