Abstract

MicroRNAs are a class of small non-protein-coding RNA transcripts that participate in the endogenous regulation of gene expression. They play important roles in both the brain and immune system and microRNA dysregulation may contribute to the pathophysiology of depression. Chronic administration of exogenous corticosterone is an established preclinical model of depression that displays behavioural abnormalities and neurochemical manifestations similar to those seen in major depressive disorder. We investigated the impact of chronic corticosterone on behaviour and hippocampal microRNA expression in rats. We randomly administered corticosterone (40 mg/kg, s.c.) or vehicle daily to male Sprague–Dawley rats ( n = 8 per group) for 21 days. Chronic corticosterone significantly decreased food intake ( p < 0.01), body-weight ( p < 0.01) and adrenal gland weight ( p < 0.001) of rats compared to vehicle controls. It also induced increased immobility in the forced swim test ( p < 0.01), a test of depressive behaviour. The expression of a panel of 768 microRNAs was measured in hippocampal total RNA run on the Applied Biosystems TaqMan® Rodent MicroRNA Array cards v3. Our results show that chronic corticosterone induced a significant change in the expression of 30 microRNAs in the hippocampus measured 24 h following the final corticosterone injection. Alterations in microRNA expression in this model may give insight into the role of microRNAs in depression.

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