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Abstinence from ethanol dependence produces concomitant cortical gray matter abnormalities, microstructural deficits

Sucharita S Somkuwar1, Emmanuel G Villalpando1, Leon W Quach1

  • 1VA San Diego Healthcare System, San Diego, CA 92161, USA.

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
|December 6, 2020
PubMed
Summary

Chronic intermittent ethanol (CIE) exposure causes aberrant myelin changes in the medial prefrontal cortex (mPFC) during abstinence. This myelin dysfunction leads to gray matter damage and impaired cognitive behaviors in rats.

Keywords:
DTIElectron microscopyFear conditioningMitochondriaMyelinPrefrontal cortex

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Area of Science:

  • Neuroscience
  • Neuroimaging
  • Cellular Biology

Background:

  • Chronic intermittent ethanol (CIE) exposure and protracted abstinence (CIE-PA) alter oligodendrogenesis in the rodent medial prefrontal cortex (mPFC).
  • CIE-PA increases premyelinating oligodendroglial progenitor cells and myelin, linked to persistent elevated drinking during abstinence.

Purpose of the Study:

  • To evaluate myelin integrity and microstructural deficits in the mPFC during abstinence following CIE exposure.
  • To investigate the association between myelin changes, brain structure, and cognitive function.

Main Methods:

  • In vivo diffusion tensor imaging (DTI) and electron microscopy were used to assess microstructural integrity in the mPFC and corpus callosum (CC).
  • Myelin-associated proteins, myelin structure, and mitochondrial stress were examined.
  • Cognitive performance was evaluated using Pavlovian fear conditioning.

Main Results:

  • DTI revealed altered microstructural integrity in the mPFC and CC.
  • Reduced fractional anisotropy (FA) in the CC and enhanced mean diffusivity (MD) in the mPFC were observed in 7-day abstinent rats.
  • Increased MD correlated with aberrant myelin increases, myelin damage, and mitochondrial stress, alongside impaired fear memory retrieval and recall.

Conclusions:

  • Forced abstinence from alcohol use disorder induces gray matter damage through myelin dysfunction in the mPFC.
  • These microstructural changes are linked to deficits in medial prefrontal cortex-dependent behaviors.