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Protracted abstinence from chronic ethanol exposure alters the structure of neurons and expression of oligodendrocytes and myelin in the medial prefrontal cortex.

Abstract：

:In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol dependence, alters the structure and activity of pyramidal neurons and decreases the number of oligodendroglial progenitors in the medial prefrontal cortex (mPFC). In this study, adult Wistar rats were exposed to seven weeks of CIE and were withdrawn from CIE for 21 days (protracted abstinence; PA). Tissue enriched in the mPFC was processed for Western blot analysis and Golgi-Cox staining to investigate the long-lasting effects of CIE on the structure of mPFC neurons and the levels of myelin-associated proteins. PA increased dendritic arborization within apical dendrites of pyramidal neurons. These changes occurred concurrently with hypophosphorylation of the N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) at Tyr-1472. PA increased myelin basic protein (MBP) levels which occurred concurrently with hypophosphorylation of the premyelinating oligodendrocyte bHLH transcription factor Olig2 in the mPFC. Given that PA is associated with increased sensitivity to stress and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and stress alters oligodendrocyte expression as a function of glucocorticoid receptor (GR) activation, the levels of total GR and phosphorylated GR were also evaluated. PA produced hypophosphorylation of the GR at Ser-232 without affecting expression of total protein. These findings demonstrate persistent and compensatory effects of ethanol in the mPFC long after cessation of CIE, including enhanced myelin production and impaired GR function. Collectively, these results suggest a novel relationship between oligodendrocytes and GR in the mPFC, in which stress may alter frontal cortex function in alcohol dependent subjects by promoting hypermyelination, thereby altering the cellular composition and white matter structure in the mPFC.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Navarro AI,Mandyam CD

doi

10.1016/j.neuroscience.2015.02.043

subject

Has Abstract

pub_date

2015-05-07 00:00:00

pages

35-44

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(15)00195-5

journal_volume

293

pub_type

杂志文章

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Protracted abstinence from chronic ethanol exposure alters the structure of neurons and expression of oligodendrocytes and myelin in the medial prefrontal cortex.