Anti-depressant effect of cerebrolysin in reserpine-induced depression in rats: Behavioral, biochemical, molecular and immunohistochemical evidence

Abstract

Depression is a major psychological disorder that contributes to global health problem. This study aimed to evaluate the anti-depressant effect of Cerebrolysin (CBL) in Reserpine-induced depressed rats, its effect on oxidative stress, inflammation, regulatory cyclic AMP-dependent response element binding protein (CREB)/brain derived neurotropic factor (BDNF) signaling pathways, brain monoamines and histopathological changes was assessed. Rats received either the vehicle or Reserpine (0.5 mg/kg, i.p.) for 14 days. The other three groups were pretreated with CBL (2.5, 5 ml/kg; i.p.) or fluoxetine (FLU) (5 mg/kg, p.o.), respectively for 14 days, 30 min before reserpine injection. Then analyses were conducted. CBL reversed Reserpine-induced reduction in latency to immobility and prolongation of immobility time in the forced swimming test (FST), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced tumor necrosis factor-alpha (TNF-ɑ), and elevated BDNF cortical and hippocampal brain contents. CBL elevated protein kinase A (PKA) and nuclear factor kappa-B (NF-κB) cortical and hippocampal protein expressions. CBL also ameliorated alterations in mRNA expressions of protein kinase B (AKT), CREB and BDNF in the cortical and hippocampal tissues. CBL elevated nor-epinephrine (NE), serotonin (5-HT), and dopamine (DA) and reduced 5-Hydroxyindoleacetic acid (5-HTAA), 3,4-Dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) cortical and hippocampal contents. CBL effects were in parallel to those observed with the standard anti-depressant drug, FLU. This study shows that CBL exerted anti-depressant effect evidenced by attenuation of oxidative stress and inflammation as well as enhancement of neurogenesis, amelioration of monoaminergic system and histopathological changes.