Zare Nayereh, Maghsoudi Nader, Mirbehbahani Seyed Hamidreza, Foolad Forough, Khakpour Shahrzad, Mansouri Zahra, Khodagholi Fariba, Ghorbani Yekta Batool
Department of Anatomical Sciences and Cognitive Neuroscience, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2022 Nov;72(11):2233-2241. doi: 10.1007/s12031-022-02062-2. Epub 2022 Sep 3.
In the last decade, there has been a great increase in methamphetamine hydrochloride (METH) abuse by pregnant women that exposes fetus and human offspring to a wide variety of developmental impairments that may be the underlying causes of future psychosocial issues. Herein, we investigated whether prenatal METH exposure with different doses (2 and 5 mg/kg) could influence neuronal cell death and antioxidant level in the different brain regions of adult male and female offspring. Adult male and female Wistar rats prenatally exposed to METH (2 or 5 mg/kg) and/or saline was used in this study. At week 12, adult rats' offspring were decapitated to collect different brain region tissues including amygdala (AMY) and prefrontal cortices (PFC). Western blot analysis was performed to evaluate the apoptosis- and autophagy-related markers, and enzymatic assay was used to measure the level of catalase and also reduced glutathione (GSH). Our results showed that METH exposure during pregnancy increased the level of apoptosis (BAX/Bcl-2 and Caspase-3) and autophagy (Beclin-1 and LC3II/LC3I) in the PFC and AMY areas of both male and female offspring's brain. Also, we found an elevation in the GSH content of all both mentioned brain areas and catalase activity of PFC in the offspring's brain. These changes were more significant in female offspring. Being prenatally exposed to METH increased cell death at least partly via apoptosis and autophagy in AMY and PFC of male and female offspring's brain, while the antioxidant system tried to protect cells in these regions.
在过去十年中，孕妇滥用盐酸甲基苯丙胺（METH）的情况大幅增加，这使胎儿和人类后代面临各种发育障碍，而这些障碍可能是未来心理社会问题的潜在原因。在此，我们研究了不同剂量（2和5毫克/千克）的产前METH暴露是否会影响成年雄性和雌性后代不同脑区的神经元细胞死亡和抗氧化水平。本研究使用了产前暴露于METH（2或5毫克/千克）和/或生理盐水的成年雄性和雌性Wistar大鼠。在第12周时，将成年大鼠的后代断头以收集不同脑区组织，包括杏仁核（AMY）和前额叶皮质（PFC）。进行蛋白质免疫印迹分析以评估凋亡和自噬相关标志物，并使用酶促测定法测量过氧化氢酶水平以及还原型谷胱甘肽（GSH）水平。我们的结果表明，孕期暴露于METH会增加雄性和雌性后代大脑PFC和AMY区域的凋亡水平（BAX/Bcl-2和Caspase-3）和自噬水平（Beclin-1和LC3II/LC3I）。此外，我们发现上述两个脑区的GSH含量以及后代大脑中PFC的过氧化氢酶活性均有所升高。这些变化在雌性后代中更为显著。产前暴露于METH至少部分通过凋亡和自噬增加了雄性和雌性后代大脑AMY和PFC中的细胞死亡，而抗氧化系统试图保护这些区域的细胞。
