☆ 4.6 Article

Reactive, Adult Neurogenesis From Increased Neural Progenitor Cell Proliferation Following Alcohol Dependence in Female Rats

FRONTIERS IN NEUROSCIENCE (2021)

期刊

FRONTIERS IN NEUROSCIENCE

卷 15, 期 -, 页码 -

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FRONTIERS MEDIA SA

DOI: 10.3389/fnins.2021.689601

关键词

alcohol; ethanol; hippocampus; abstinence; recovery; alcoholism; adult neurogenesis; neural stem cells

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Neurosciences

资金

NIH [R01AA025591, R01AA016959, R21AA025563, T32AA007471]
University of Texas at Austin

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Recent studies suggest that females may be more susceptible to alcohol-induced brain damage, and during abstinence from alcohol dependence, adult female rats also exhibit similar reactive increases in hippocampal neurogenesis. These data suggest that reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

Hippocampal neurodegeneration is a consequence of excessive alcohol drinking in alcohol use disorders (AUDs), however, recent studies suggest that females may be more susceptible to alcohol-induced brain damage. Adult hippocampal neurogenesis is now well accepted to contribute to hippocampal integrity and is known to be affected by alcohol in humans as well as in animal models of AUDs. In male rats, a reactive increase in adult hippocampal neurogenesis has been observed during abstinence from alcohol dependence, a phenomenon that may underlie recovery of hippocampal structure and function. It is unknown whether reactive neurogenesis occurs in females. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by 7 or 14 days of abstinence. Immunohistochemistry (IHC) was used to assess neural progenitor cell (NPC) proliferation (BrdU and Ki67), the percentage of increased NPC activation (Sox2+/Ki67+), the number of immature neurons (NeuroD1), and ectopic dentate gyrus granule cells (Prox1). On day seven of abstinence, ethanol-treated females showed a significant increase in BrdU+ and Ki67+ cells in the subgranular zone of the dentate gyrus (SGZ), as well as greater activation of NPCs (Sox2+/Ki67+) into active cycling. At day 14 of abstinence, there was a significant increase in the number of immature neurons (NeuroD1+) though no evidence of ectopic neurogenesis according to either NeuroD1 or Prox1 immunoreactivity. Altogether, these data suggest that alcohol dependence produces similar reactive increases in NPC proliferation and adult neurogenesis. Thus, reactive, adult neurogenesis may be a means of recovery for the hippocampus after alcohol dependence in females.

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EGFL7 loss correlates with increased VEGF-D expression, upregulating hippocampal adult neurogenesis and improving spatial learning and memory

Kathrin Barth, Verica Vasic, Brennan McDonald, Nora Heinig, Marc-Christoph Wagner, Ulrike Schumann, Cora Roehlecke, Frank Bicker, Lana Schumann, Konstantin Radyushkin, Jan Baumgart, Stefan Tenzer, Frauke Zipp, Matthias Meinhardt, Kari Alitalo, Irmgard Tegeder, Mirko H. H. Schmidt

Summary: Mature neurons, neural stem cells, and neural precursor cells secrete the neurovascular protein EGFL7 to shape the neurogenic niche of the hippocampus. Ablation of EGFL7 leads to increased neurogenesis and is correlated with elevated expression of VEGF-D. Infusion of VEGF-D increases neurogenesis, while its knockout decreases neurogenesis. Furthermore, EGFL7 knockout mice show improved spatial memory and memory consolidation in the hippocampus.

CELLULAR AND MOLECULAR LIFE SCIENCES (2023)