Early maternal separation potentiates the impact of later social isolation in inducing depressive-like behavior via oxidative stress in adult rats.

RATIONALE

Individuals who have experienced early life stress (ELS) are more vulnerable to later life stress induced depression, which might attribute to ELS potentiated impact of later life stress. The presumption and neurobiological mechanisms involved require further validation and elucidation.

OBJECTIVES

To investigate impact of pre-weaning maternal separation (MS) on post-weaning social isolation (SI) in inducing depressive-like behavior, and involvement of central oxidative stress, glutamatergic and brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling in the process.

METHODS

Male offspring were exposed to MS, SI or maternal separation and social isolation (MSSI) stress, respectively. Subjects were treated with saline, antioxidant diallyl disulfide (DADS) (30 mg/kg, i.g.) or antidepressant fluoxetine (10 mg/kg, i.p.), for two weeks before behavioral tests in adolescents or adults. Depressive-like behavior was assessed with sucrose preference, forced swim and tail suspension tests. Concentrations of 4-hydroxynonenal (4-HNE), glutathione and superoxide dismutase in hippocampus and serum, and hippocampal protein expressions of glutamate transporter 1 (GLT-1), BDNF and TrkB were assessed by western blotting analysis.

RESULTS

MSSI, rather than MS or SI, induced significant depressive-like behavior, in adults but not adolescents. Consistently, only MSSI significantly elevated 4-HNE, whereas inhibited GLT-1, BDNF and TrkB in adult hippocampus. MSSI induced behavioral and biochemical abnormalities in adults were reversed by DADS or fluoxetine treatment.

CONCLUSIONS

Early MS age-dependently potentiates later SI impact in inducing depressive-like behavior in male rats, through elevating oxidative stress and interrupting glutamatergic and BDNF/TrkB signaling in the brain. Results further suggest antioxidant treatment as a promising anti-depressant avenue.