Neonatal Stress Alters Social Behavior And Bdnf Levels In The Cortex And Hippo-Campus Of Adult Balb/Cbyj Mice
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Neonatal stress and trauma are risk factors for mental health disorders such as autism, schizophrenia, and depression, which are characterized by altered social behavior, and brain-derived neurotrophic factor (BDNF) expression. BDNF has a crucial regulatory role in morphogenesis and neuroplasticity of the developing brain, particularly in the hippocampus and cerebral cortex, which are highly influenced by cortisol/corticosterone (CORT) levels. Previously, our laboratory has shown alteration of development and plasticity of the cerebral cortex as a result of neonatal stress. This thesis examines, whether neonatally stressed Balb/CByJ mice exhibit altered social behavior and BDNF levels in cortex/hippocampus in adulthood. In a split litter design, half of the pups (STR) were removed from dams for 1hr/day from postnatal day (PND) 2 to 7, and exposed for 30 minutes to cold (4 oC) or hot (37 oC) stress on alternating days, whereas littermates (LMC) remained with the dam. A cohort of age-matched, colony-reared mice (AMC) also served as controls. Thirty adult male mice, (10 STR, 10 LMC and 10 AMC) were tested in a three-chambered automated apparatus developed by J. Crawley (Crawley 2004). Detailed analyses of video-taped recordings, using CleverSys software, showed that STR males exhibited significantly less social interaction and exploratory behavior than AMC and LMC males, respectively, with significantly higher repetitive behavior (self-grooming) in STR mice. Following behavioral testing, brains were analyzed for BDNF levels by Western blotting. The results showed significantly lower mature BDNF (mBDNF) levels in the cortex as well as hippocampus of STR mice, compared to LMC. In contrast, a significantly higher precursor BDNF/mBDNF ratio was observed in the hippocampus, and a similar trend was seen in the cortex of STR compared to AMC and LMC mice. Thus, altered processing of BDNF in the adult hippocampus and cortex, following neonatal stress may permanently alter morphology and plasticity in these regions and consequently impair social and exploratory behaviors in adulthood.