Spatial and Sex-Dependent Responses of Adult Endogenous Neural Stem Cells to Alcohol Consumption

Stem Cell Reports. 2017 Dec 12;9(6):1916-1930. doi: 10.1016/j.stemcr.2017.10.007. Epub 2017 Nov 9.

Abstract

Chronic alcohol abuse results in alcohol-related neurodegeneration, and critical gaps in our knowledge hinder therapeutic development. Neural stem cells (NSCs) are a subpopulation of cells within the adult brain that contribute to brain maintenance and recovery. While it is known that alcohol alters NSCs, little is known about how NSC response to alcohol is related to sex, brain region, and stage of differentiation. Understanding these relationships will aid in therapeutic development. Here, we used an inducible transgenic mouse model to track the stages of differentiation of adult endogenous NSCs and observed distinct NSC behaviors in three brain regions (subventricular zone, subgranular zone, and tanycyte layer) after long-term alcohol consumption. Particularly, chronic alcohol consumption profoundly affected the survival of NSCs in the subventricular zone and altered NSC differentiation in all three regions. Significant differences between male and female mice were further discovered.

Keywords: chronic alcohol; neural stem cell; neuronal differentiation; sex differences; subgranular zone; subventricular zone; tanycyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects
  • Alcohol Drinking / genetics
  • Alcohol Drinking / physiopathology*
  • Alcohols / toxicity
  • Animals
  • Brain Mapping
  • Cell Differentiation / drug effects
  • Disease Models, Animal
  • Female
  • Lateral Ventricles / drug effects
  • Lateral Ventricles / physiopathology*
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology*
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / pathology
  • Neurons / drug effects
  • Neurons / pathology

Substances

  • Alcohols