Fatehfar Sina, Sameei Parsa, Abdollahzade Naseh, Chodari Leila, Saboory Ehsan, Roshan-Milani Shiva
Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.
School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Dev Neurobiol. 2025 Apr;85(2):e22964. doi: 10.1002/dneu.22964.
The detrimental effects of prenatal stress (PS) on offspring's neurological and behavioral outcomes are well documented. However, strategies to mitigate these effects are underexplored. This study examines whether prenatal zinc supplementation and treadmill exercise can modulate PS-induced cognitive impairments and neurobiological markers in young and adult male rat offspring, leveraging the established neuroprotective potential of both physical activity and zinc. Pregnant rats were divided into five groups: control, stress, stress + exercise, stress + zinc, and stress + exercise + zinc, with all rats except the control group subjected to restraint stress (gestational days 15-19). Pregnant rats in the exercise groups underwent forced exercise, whereas those in the zinc groups received oral zinc sulfate throughout the pregnancy. At postnatal days 30 and 90, the cognitive function of male offspring was evaluated using the Morris water maze (MWM) test, and the hippocampal gene expression levels of caspase-3, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) were measured using reverse transcription-polymerase chain reaction (RT-PCR). PS impaired cognitive functions, increased caspase-3 expression, and decreased BDNF and GFAP expression levels in adult rats. Prenatal exercise was found to mitigate PS-induced cognitive deficits primarily through enhancing GFAP expression, whereas prenatal zinc improved PS-induced cognitive impairments mainly through reduced caspase-3 and increased BDNF expression. The combined effect of exercise and zinc was not additive on cognitive functions and biomarkers. Physical activity may alleviate PS-induced cognitive deficits by modulating astrocytic factors, whereas zinc may exert its effects by inhibiting apoptosis via a BDNF-dependent pathway. Further targeted research is necessary to confirm these relationships.
产前应激（PS）对后代神经和行为结果的有害影响已有充分记录。然而，减轻这些影响的策略尚未得到充分探索。本研究利用已确立的体育活动和锌的神经保护潜力，探讨产前补充锌和跑步机运动是否能调节PS诱导的年轻和成年雄性大鼠后代的认知障碍和神经生物学标志物。将怀孕大鼠分为五组：对照组、应激组、应激 + 运动组、应激 + 锌组和应激 + 运动 + 锌组，除对照组外，所有大鼠均受到束缚应激（妊娠第15 - 19天）。运动组的怀孕大鼠进行强迫运动，而锌组的大鼠在整个孕期接受口服硫酸锌。在出生后第30天和第90天，使用莫里斯水迷宫（MWM）试验评估雄性后代的认知功能，并使用逆转录 - 聚合酶链反应（RT-PCR）测量海马中半胱天冬酶 - 3、脑源性神经营养因子（BDNF）和胶质纤维酸性蛋白（GFAP）的基因表达水平。PS损害了成年大鼠的认知功能，增加了半胱天冬酶 - 3的表达，并降低了BDNF和GFAP的表达水平。发现产前运动主要通过增强GFAP表达来减轻PS诱导的认知缺陷，而产前锌主要通过降低半胱天冬酶 - 3和增加BDNF表达来改善PS诱导的认知障碍。运动和锌对认知功能和生物标志物的联合作用不是相加的。体育活动可能通过调节星形细胞因子来减轻PS诱导的认知缺陷，而锌可能通过BDNF依赖性途径抑制细胞凋亡来发挥其作用。需要进一步的针对性研究来证实这些关系。
