Erdogan Mumin Alper, Turk Miray, Doganay Gizem Dinler, Sever Ibrahim Halil, Ozkul Bahattin, Sogut Ibrahim, Eroglu Ebru, Uyanikgil Yigit, Erbas Oytun
Faculty of Medicine, Department of Physiology, Izmir Katip Celebi University, Izmir, Turkey.
Graduate School, Department of Molecular Biology-Genetics and Biotechnology, Istanbul Technical University, 34469, Istanbul, Turkey.
J Neuroimmune Pharmacol. 2023 Dec;18(4):573-591. doi: 10.1007/s11481-023-10089-4. Epub 2023 Oct 27.
Recent research on placental, embryo, and brain organoids suggests that the COVID-19 virus may potentially affect embryonic organs, including the brain. Given the established link between SARS-CoV-2 spike protein and neuroinflammation, we sought to investigate the effects of exposure to this protein during pregnancy. We divided pregnant rats into three groups: Group 1 received a 1 ml/kg saline solution, Group 2 received 150 μg/kg adjuvant aluminum hydroxide (AAH), and Group 3 received 40 μg/kg spike protein + 150 μg/kg AAH at 10 and 14 days of gestation. On postnatal day 21 (P21), we randomly separated 60 littermates (10 male-female) into control, AAH-exposed, and spike protein-exposed groups. At P50, we conducted behavioral analyses on these mature animals and performed MR spectroscopy. Subsequently, all animals were sacrificed, and their brains were subject to biochemical and histological analysis. Our findings indicate that male rats exposed to the spike protein displayed a higher rate of impaired performance on behavioral studies, including the three-chamber social test, passive avoidance learning analysis, open field test, rotarod test, and novelty-induced cultivation behavior, indicative of autistic symptoms. Exposure to the spike protein (male) induced gliosis and neuronal cell death in the CA1-CA3 regions of the hippocampus and cerebellum. The spike protein-exposed male rats exhibited significantly greater levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and lactate and lower levels of brain-derived neurotrophic factor (BDNF) than the control group. Our study suggests a potential association between prenatal exposure to COVID-19 spike protein and neurodevelopmental problems, such as ASD. These findings highlight the importance of further research into the potential effects of the COVID-19 virus on embryonic and fetal development and the potential long-term consequences for neurodevelopment.
近期对胎盘、胚胎和脑类器官的研究表明，新冠病毒可能会影响包括大脑在内的胚胎器官。鉴于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白与神经炎症之间已确定的联系，我们试图研究孕期接触该蛋白的影响。我们将怀孕大鼠分为三组：第1组接受1毫升/千克的盐溶液，第2组接受150微克/千克的佐剂氢氧化铝（AAH），第3组在妊娠第10天和第14天接受40微克/千克的刺突蛋白 + 150微克/千克的AAH。在出生后第21天（P21），我们将60只同窝幼崽（10对雌雄）随机分为对照组、暴露于AAH组和暴露于刺突蛋白组。在P50时，我们对这些成熟动物进行行为分析并进行磁共振波谱分析。随后，处死所有动物，并对其大脑进行生化和组织学分析。我们的研究结果表明，暴露于刺突蛋白的雄性大鼠在行为研究中表现出更高的行为受损率，包括三室社交试验、被动回避学习分析、旷场试验、转棒试验和新奇诱导的探索行为，这表明存在自闭症症状。暴露于刺突蛋白（雄性）会在海马体和小脑的CA1-CA3区域诱导神经胶质增生和神经元细胞死亡。与对照组相比,暴露于刺突蛋白的雄性大鼠表现出显著更高水平的丙二醛（MDA）、肿瘤坏死因子α（TNF-α）、白细胞介素-17（IL-17）、核因子κB（NF-κB）和乳酸，以及更低水平的脑源性神经营养因子（BDNF）。我们的研究表明，产前接触新冠病毒刺突蛋白与神经发育问题（如自闭症谱系障碍）之间可能存在关联。这些发现凸显了进一步研究新冠病毒对胚胎和胎儿发育的潜在影响以及对神经发育潜在长期后果的重要性。
