title: Impact of combined prenatal ethanol and prenatal stress exposures on markers of activity-dependent synaptic plasticity in rat dentate gyrus.
abstract: Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression of AMPA-glutamate receptor subunits (GluA1 and GluA2) in dentate gyrus of female adult offspring under baseline conditions and after 2-trial trace conditioning (TTTC). Surprisingly, baseline cytoplasmic ARC expression was significantly elevated in both prenatal treatment groups. In contrast, synaptosomal GluA1 receptor subunit expression was decreased in both prenatal treatment groups. GluA2 subunit expression was elevated in the prenatal stress group. TTTC did not alter ARC levels compared to an unpaired behavioral control (UPC) group in any of the 4 prenatal treatment groups. In contrast, TTTC significantly elevated both synaptosomal GluA1 and GluA2 subunit expression relative to the UPC group in control offspring, an effect that was not observed in any of the other 3 prenatal treatment groups. Given ARC's role in regulating synaptosomal AMPA receptors, these results suggest that prenatal ethanol-induced or prenatal stress exposure-induced increases in baseline ARC levels could contribute to reductions in both baseline and activity-dependent changes in AMPA receptors in a manner that diminishes the role of AMPA receptors in dentate gyrus synaptic plasticity and hippocampal-sensitive learning.
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Staples
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Morgan W
authors.initials: MW
authors.lastname: Porch
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Electronic address: DSavage@salud.unm.edu.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Savage
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000032:analysis; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009473:Neuronal Plasticity / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000032:analysis / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D003598:Cytoskeletal Proteins; D000431:Ethanol; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C092069:activity regulated cytoskeletal-associated protein; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA receptor; ARC; Fetal alcohol spectrum disorder; Prenatal stress; Western blot