Neuroprotective Effects of Carnosine Against Corticosterone-Induced Depression and Memory Impairment

Corticosterone (Crt) is reported to induce oxidative stress in experimental animals. Carnosine (Crn), a well-known dipeptide antioxidant synthesized endogenously from β-alanine and L-histidine, neutralizes oxidative stress. The current study examines the influences of Crn on Crt-induced behavioral alterations (depressive-like behaviors and cognitive performance), oxidative damage, antioxidant enzymes activity, inflammatory markers, serotonin metabolism, and histopathology in female rats. Thirty-six animals were allocated to six groups (n = 6): (i) vehicle (vh) + vh (1 mg/kg) (ii) vh + Crn (20 mg/kg), (iii) vh + Crn (50 mg/kg), (iv) vh + Crt (20 mg/kg) (v) Crt + Crn (20 mg/kg), and (vi) Crt + Crn (50 mg/kg). All respective doses were given intraperitoneally (i.p) for 2 weeks. After treatment, behavioral testing was done via the Tail suspension test (TST) for depressive-like behavior and the Morris Water Maze (MWM) for spatial memory. Crn treatment had significant effects on Crt-induced behavioral impairments, such as depressive-like behavior and cognitive dysfunction. After completing behavioral tests, the rats underwent decapitation, and the hippocampus was separated for further biochemical and neurochemical analyses. Outcomes revealed that Crn mitigates depressive-like behaviors and cognitive dysfunction. Crn reduces oxidative stress and inflammatory cytokine levels while improving antioxidant enzyme activity, restoring cholinergic and serotonergic transmission, and brain (hippocampus) morphology following Crt-administration. The in silico analyses also demonstrate its strong binding affinity with monoamine oxidases (MAO) A and B, with an energy of -7.1 and -6.7 kcal/mol, respectively. In conclusion, the present results showed that Crn possesses strong antioxidant properties and reduced Crt-induced depressive-like behavior and memory impairment due to its effective abilities as antioxidant and neuromodulator. Supplementation with Crn as a dietary component may provide protective benefits against Crt-induced depression-like behavior and memory impairment.