Sex-specific deficits in biochemical but not behavioral responses to delay fear conditioning in prenatal alcohol exposure mice.

摘要: Abstract Background Studies in clinical populations and preclinical models have shown that prenatal alcohol exposure (PAE) is associated with impairments the acquisition, consolidation recall of information, deficits hippocampal formation-dependent learning memory being a common finding. The glucocorticoid receptor (GR), mineralocorticoid (MR), extracellular signal-regulated kinase 2 (ERK2) are key regulators formation development, structure functioning and, thus, potential mediators PAE’s effects on this brain region. In present studies, we employed well-characterized mouse model PAE to identify biochemical mechanisms may underlie activity-dependent PAE. Methods Mouse dams consumed either 10% (w/v) ethanol 0.066% saccharin (SAC) or SAC alone using limited (4-h) access, drinking-in-the-dark paradigm. Male female offspring (∼180-days age) were trained delay conditioning procedure contextual fear responses (freezing behavior) measured 24 h later. Hippocampal tissue blood collected from three behavioral groups animals: 20 min following (conditioning only group), re-exposure context plus behaviorally naive (naive group) mice. Plasma corticosterone levels by enzyme immunoassay. Immunoblotting techniques used measure protein GR, MR, ERK1 ERK2 nuclear membrane fractions prepared formation. Results Adult control male mice displayed similar fear. However, significant sex differences observed freezing exhibited during session. Compared same-sex controls, demonstrated While plasma concentrations elevated males females relative their respective animals. Relative group, GR increased SAC, but not PAE, group. contrast, no difference was between groups. females, significantly reduced there effect group interaction treatment males, MR compared both Levels activated (phospho-ERK2 expressed total ERK2) re-exposure, found. No main interactions found These findings suggest which molecular pathways Conclusions loss responsiveness signals generated re-exposure. deficit does appear be changes activation training recall, although an overall reduction play role. studies add growing body literature demonstrating that, at least partially, different learning, these differentially affected