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Structural reorganization of pyramidal neurons in the medial prefrontal cortex of alcohol dependent rats is associated with altered glial plasticity

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Abstract

In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol dependence, alters the activity of pyramidal neurons and decreases the number of glial progenitors in the medial prefrontal cortex (mPFC). Adult male Wistar rats were exposed to CIE and were injected with mitotic markers to label and phenotype proliferating cells to test the hypothesis that CIE produces concurrent alterations in the structure of pyramidal neurons and the cell cycle kinetics and developmental stages of glial progenitors in the mPFC. Medial prefrontal cortical tissue was processed for Golgi-Cox staining, immunohistochemistry and Western blotting analysis. CIE increased dendritic arborization and spine densities within basal and apical dendrites of pyramidal neurons via aberrant reorganization of actin cytoskeleton-associated molecules. CIE concomitantly increased the expression of total NR2B subunits without affecting phosphorylation of NR2B at Tyr-1472 or levels of PSD-95. CIE reduced the length of S-phase of the cell cycle of glial progenitors and reduced proliferation and differentiation of progenitors into bHLH transcription factor Olig2-expressing premyelinating oligodendrocyte progenitor cells (OPCs). CIE also produced a corresponding hyperphosphorylation of Olig2, and reduced expression of myelin basic protein. Our findings demonstrate that CIE-induced alterations in OPCs and myelin-related proteins are associated with profound alterations in the structure of pyramidal neurons. In sum, our results not only provide evidence that alcohol dependence leads to pathological changes in the mPFC, which may in part define a cellular basis for cognitive impairments associated with alcoholism, but also show dependence-associated morphological changes in the PFC at the single neuron level.

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Acknowledgments

The study was supported by funds from the National Institute on Drug Abuse (DA022473 to CDM), National institute on Alcoholism and Alcohol Abuse (AA020098 and AA06420 to CDM, AA020839 to SE) and Alcohol Beverage Medical Research Foundation to CDM. The authors thank Drs. Charles Stiles and John Alberta, Harvard Medical School, for generously providing Olig2 and phosphorylated Olig2 antibodies. We thank Dr. Heidi Jurgens, University of Illinois, for her assistance with the dendritic arborization analysis and spine density analysis. We appreciate the technical support of Elena Crawford for immunohistochemical analyses, StereoInvestigator and Neurolucida, and Maury Cole for assistance with alcohol vapor chambers. We thank Drs. Miranda Staples and Florence Varodayan for critical reading of the manuscript and McKenzie Fannon for editorial assistance. This is publication number 25057 from The Scripps Research Institute.

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  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA

    Airee Kim, Eva R. Zamora-Martinez & Chitra D. Mandyam

  2. Department of Physiology, Alcohol and Drug Abuse Center of Excellence, LSU Health Sciences Center, New Orleans, LA, USA

    Scott Edwards

  3. Skaggs School of Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA

    Chitra D. Mandyam

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  1. Airee Kim
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  2. Eva R. Zamora-Martinez
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Correspondence to Chitra D. Mandyam.

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Kim, A., Zamora-Martinez, E.R., Edwards, S. et al. Structural reorganization of pyramidal neurons in the medial prefrontal cortex of alcohol dependent rats is associated with altered glial plasticity. Brain Struct Funct 220, 1705–1720 (2015). https://doi.org/10.1007/s00429-014-0755-3

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  • DOI: https://doi.org/10.1007/s00429-014-0755-3

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