title: Structural reorganization of pyramidal neurons in the medial prefrontal cortex of alcohol dependent rats is associated with altered glial plasticity.
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.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA.
authors.forename: Airee
authors.initials: A
authors.lastname: Kim
authors.forename: Eva R
authors.initials: ER
authors.lastname: Zamora-Martinez
authors.forename: Scott
authors.initials: S
authors.lastname: Edwards
authors.forename: Chitra D
authors.initials: CD
authors.lastname: Mandyam
mesh_terms: D000280:Administration, Inhalation; D000437:Alcoholism / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D049229:Dendritic Spines / Q000473:pathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000076122:Disks Large Homolog 4 Protein; D000431:Ethanol; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D016194:Receptors, N-Methyl-D-Aspartate; C501449:Dlg4 protein, rat; C121001:NR2B NMDA receptor; C522729:Olig2 protein, rat