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

ABSTRACT 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.