Mohamadi Yarijani Zeynab, Raise-Abdullahi Payman, Parsaei Houman, Ghanbari Ali, Meamar Morvarid, Yousefi Behpour, Madanchi Hamid, Rashidy-Pour Ali
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Int J Biol Macromol. 2025 Sep;321(Pt 3):146498. doi: 10.1016/j.ijbiomac.2025.146498. Epub 2025 Aug 4.
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.
本研究旨在评估菠萝蛋白酶消化的酪蛋白肽库（BDCPP）对雄性大鼠慢性应激诱导的行为、生化、分子和组织学变化的治疗效果。BDCPP是一种对红细胞、U87 MG细胞和HepG2细胞无毒的化合物。将Wistar大鼠进行慢性应激实验，并口服BDCPP进行治疗。行为评估包括高架十字迷宫（EPM）、明暗箱试验（L/D）、强迫游泳试验（FST）、莫里斯水迷宫（MWM）和T迷宫。生化检测测量皮质酮、丙二醛（MDA）、超氧化物歧化酶（SOD）和总抗氧化能力（TAC）水平。进行蛋白质免疫印迹法以评估海马脑源性神经营养因子（BDNF）和胰岛素样生长因子1（IGF-1）的表达。使用高尔基-考克斯染色法，组织学评估聚焦于海马体（CA3区）和基底外侧杏仁核（BLA）的树突形态。给予BDCPP可改善焦虑和抑郁样行为，使皮质酮水平正常化，增强抗氧化能力，并增加海马体中BDNF和IGF-1的表达。BDCPP减轻了应激诱导的CA3锥体神经元树突回缩，并减轻了BLA神经元的肥大。BDCPP对慢性应激诱导的行为和神经生物学损伤具有有益作用，特别是通过调节海马体和杏仁核的可塑性。这些发现突出了其作为基于功能性食品的应激相关疾病干预措施的潜力。
