BDNF levels in the rat prefrontal cortex, amygdala and hippocampal CA3 region in an animal model of mania
Background: Studies have shown that neurotrophins are involved in the pathophysiology of bipolar disorder (BD). For instance, serum brain-derived neurotrophic factor (BDNF) levels are decreased in manic and depressed patients with BD compared with patients during euthymia and controls. There are evidences that first line mood stabilizers may increase the expression of neurotrophic factors. Objective: We aim to investigate the effects of lithium and valproate and of sodium butyrate, a histone deacetylase inhibitor similar to valproate, on mRNA and protein BDNF levels in an animal model of mania induced by D-amphetamine. Methods: Adult Wistar rats received intraperitoneal injections of D-amphetamine or saline for 14 days and, between day 8 and 14, they received also either litium, valproate, sodium butyrate or saline (n = 12 per group). Relative quantification by Real time RT-PCR and sandwich ELISA were used to measure BDNF gene expression and protein levels in rat prefrontal cortex, amygdala and hippocampal CA3 region. Results: BDNF mRNA and protein levels were not significantly different (p>0.05) between treatment groups in this model. BDNF protein levels were higher in CA3 region when compared with prefrontal cortex and amygdala in the control group. Conclusion: Controversial results of BDNF levels in the different brain regions in an animal model of mania and these negative findings may reflect the complex regulation of neurotrophins signaling system. Therefore, replication studies are needed to clarify the association of the effect of mood stabilizers and expression of BDNF in BD.