Bromelain-digested casein peptide pool mitigates stress-induced neural and behavioral deficits in rats

This study aimed to evaluate the therapeutic effects of a bromelain-digested casein peptide pool (BDCPP) on behavioral, biochemical, molecular, and histological changes induced by chronic stress in male rats. BDCPP is a non-toxic compound against erythrocyes, U87 MG, and HepG2 cells. Wistar rats were subjected to a chronic stress protocol and treated orally with BDCPP. Behavioral assessments included the elevated plus maze (EPM), Light/Dark (L/D), forced swim test (FST), Morris water maze (MWM), and T-Maze. Biochemical assays measured corticosterone, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAC) levels. Western blotting was performed to assess the expression of hippocampal brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Using Golgi-Cox staining, histological evaluations focused on dendritic morphology in the hippocampus (CA3 region) and basolateral amygdala (BLA). BDCPP administration improved anxiety and depression-like behaviors, normalized corticosterone levels, enhanced antioxidant capacity, and increased the expression of BDNF and IGF-1 in the hippocampus. BDCPP attenuated stress-induced dendritic retraction in CA3 pyramidal neurons and mitigated hypertrophy in BLA neurons. BDCPP exerts beneficial effects against chronic stress-induced behavioral and neurobiological impairments, particularly by modulating the plasticity of the hippocampus and amygdala. These findings highlight its potential as a functional food-based intervention for stress-related disorders.