[Neural network abnormalities caused by alcohol: approach for repair using neural stem cells]

Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Apr;28(2):69-73.
[Article in Japanese]

Abstract

Recent clinical neuroimaging studies have revealed the possible relation between morphological brain changes, and memory, cognitive impairment in the course of alcoholism and depression. In the previous studies, we have been analyzing the mechanism of neural network disruption by ethanol using postmortem human brain and cultured cells, and identified the sensitive effect of ethanol on the neural stem cell (NSC) differentiation rather than the influence on neuronal cell survival. Furthermore, to develop a novel method for reconstruction of the neural network damaged by ethanol, we tried to analyze the usefulness of intravenous NSC transplantation in fetal alcohol syndrome spectrum disorder (FASD) model rats. In the in vitro studies, we have found the suppressive effect of ethanol on NSC differentiation to neurons, through alteration of transcription factor, CREB and NRSF/REST activities, by the cellular signaling cascade changes including trophic factors and endoplasmic reticulum (ER) function. In the in vivo studies, we have shown the effective migration of labeled NSCs into the brain of FASD model rats, and revealed the therapeutic potential of this transplantation for the treatment of anxiety/cognitive dysfunction and behavioral abnormalities in alcohol-induced brain neural network damage. We are going to the next step for analysis of transplanted NSC dynamics in the brain, which must play a pivotal role in the effective induction of behavioral recoveries.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Alcohol Drinking
  • Alcoholism / complications
  • Alcoholism / pathology*
  • Animals
  • Brain / drug effects*
  • Brain / pathology*
  • Cell Differentiation / drug effects
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Disease Models, Animal
  • Ethanol / adverse effects*
  • Humans
  • Memory Disorders / etiology
  • Memory Disorders / pathology
  • Nerve Net / drug effects*
  • Nerve Net / pathology*
  • Neurons / cytology
  • Rats
  • Repressor Proteins / metabolism
  • Stem Cells / cytology

Substances

  • Cyclic AMP Response Element-Binding Protein
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Ethanol