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1- Department of Biology, College of Sciences, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
2- Department of Biology, College of Sciences, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.
Abstract:  
Introduction: Uteroplacental insufficiency (UPI) produces critical neurodevelopmental problems affecting the intrauterine growth restricted (IUGR) in offspring. In this study, it was aimed to investigate the possible neuroprotective roles of hesperidin (Hes) on the fetal cerebral cortex of the UPI rat model.
Methods: In this experimental study, 40 pregnant Wistar rats (age:~40-day old, weight: 180±10g) were randomly divided into 5 groups (n=8), includeing control (normal saline, orally), UPI+NS (uterine vessel ligation+normal saline, orally), UPI+HES25, UPI+HES50 and UPI+HES100 (uterine vessel ligation+25, 50 and 100 mg/kg hesperidin, orally). After being anesthetized by ketamine and xylazine, UPI was induced by permanent bilateral closure of the uterine vessels on gestation day (GD) 18. From GD15, the Hes/NS- treated groups received Hesperidin/normal saline until GD21. On GD21, uterus, placenta and fetus were dissected out and weighed. The oxidative stress parameters, including catalase (CAT) activity, malondialdehyde (MDA), and total antioxidant capacity (TAC) in the fetal cerebral cortex were measured. The expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) was assessed by RT qPCR methods. Data were analyzed by ANOVA and Tukey’s post hoc test.
Results: Findings showed a significant difference in the uterine and fetus weight in Hes-treated mothers (p< 0.05). In fetus, Hes reduced MDA, and increased CAT activity and TAC (p ˂ 0.001 in the UPI+Hes100 group compared to the UPI+NS group). UPI reduced BDNF and TrkB mRNA expression compared to the control group (p< 0.05). Also, Significant increases in BDNF and TrkB mRNA expression were observed after administration of Hes in the fetal cerebral cortex of the UPI rat model, in a dose dependent manner (p< 0.05).
Conclusion: Hesperidin; as a neuroprotective and antioxidant agent; accelerates BDNF-TrkB signaling pathway and suppresses oxidative stress parameters in the cerebral cortex of the UPI rat model.
Type of Study: Original | Subject: Cognitive Neuroscience
Received: 2019/11/9 | Accepted: 2020/05/18

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