title: Overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure.
abstract: Neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF-) or control Green Fluorescent Protein (GFP). After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF- or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD.
authors: Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0709, USA.
authors: A P
authors: AP
authors: Paul
authors: A E
authors: AE
authors: Medina
mesh_terms: D000367:Age Factors; D020751:Alcohol-Induced Disorders / Q000097:blood / Q000628:therapy*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism* / Q000637:transplantation; D001921:Brain / Q000166:cytology; D017690:Cell Transplantation; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004195:Disease Models, Animal; D023882:Dominance, Ocular; D000431:Ethanol / Q000009:adverse effects*; D005289:Ferrets; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D012845:Sindbis Virus / Q000235:genetics; D014162:Transfection; D014746:Vimentin / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D005904:Glial Fibrillary Acidic Protein; D017405:Herpes Simplex Virus Protein Vmw65; D026362:Serum Response Factor; D014746:Vimentin; D049452:Green Fluorescent Proteins; D000431:Ethanol