title: Dendritic remodeling of hippocampal neurons is associated with altered NMDA receptor expression in alcohol dependent rats.
abstract: Prolonged alcohol exposure has been previously shown to impair the structure and function of the hippocampus, although the underlying structural and biochemical alterations contributing to these deleterious effects are unclear. Also unclear is whether these changes persist into prolonged periods of abstinence. Previous work from our lab utilizing a clinically relevant rodent model of alcohol consumption demonstrated that alcohol dependence (induced by chronic intermittent ethanol vapor exposure or CIE) decreases proliferation and survival of neural stem cells in the hippocampal subgranular zone and hippocampal neurogenesis in the dentate gyrus, implicating this region of the cortex as particularly sensitive to the toxic effects of prolonged ethanol exposure. For this study, we investigated seven weeks of CIE-induced morphological changes (dendritic complexity and dendritic spine density) of dentate gyrus (DG) granule cell neurons, CA3, and CA1 pyramidal neurons and the associated alterations in biochemical markers of synaptic plasticity and toxicity (NMDA receptors and PSD-95) in the hippocampus in ethanol-experienced Wistar rats 3h (CIE) and 21days (protracted abstinence) after the last ethanol vapor exposure. CIE reduced dendritic arborization of DG neurons and this effect persisted into protracted abstinence. CIE enhanced dendritic arborization of pyramidal neurons and this effect did not persist into protracted abstinence. The architectural changes in dendrites did not correlate with alterations in dendritic spine density, however, they were associated with increases in the expression of pNR2B, total NR2B, and total NR2A immediately following CIE with expression levels returning to control levels in prolonged abstinence. Overall, these data provide the evidence that CIE produces profound changes in hippocampal structural plasticity and in molecular tools that maintain hippocampal structural plasticity, and these alterations may underlie cognitive dysfunction associated with alcohol dependence. In addition, the compensatory state concurrent with reduced plasticity during protracted abstinence could leave the hippocampus vulnerable to subsequent insult following chronic ethanol exposure.
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: Miranda C
authors.initials: MC
authors.lastname: Staples
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.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA. Electronic address: cmandyam@scripps.edu.
authors.forename: Chitra D
authors.initials: CD
authors.lastname: Mandyam
mesh_terms: D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000473:pathology*; D018891:Dentate Gyrus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
keywords: Alcoholism; Hippocampus; NMDA receptor; Prolonged abstinence; Structural plasticity