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.

Graphical Abstract

中文翻译：

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产前 SARS-CoV-2 刺突蛋白暴露可诱导雄性新生大鼠出现类似自闭症的神经行为变化

最近对胎盘、胚胎和大脑类器官的研究表明，COVID-19 病毒可能会影响胚胎器官，包括大脑。鉴于 SARS-CoV-2 刺突蛋白与神经炎症之间已确定的联系，我们试图研究怀孕期间接触该蛋白的影响。我们将怀孕大鼠分为三组：第 1 组接受 1 ml/kg 盐水溶液，第 2 组接受 150 μg/kg 佐剂氢氧化铝 (AAH)，第 3 组接受 40 μg/kg 刺突蛋白 + 150 μg/kg AAH。怀孕10天和14天。在出生后第 21 天 (P21)，我们将 60 只同窝仔猪（10 只雄性 - 雌性）随机分为对照组、AAH 暴露组和刺突蛋白暴露组。在 P50 时，我们对这些成熟动物进行了行为分析并进行了磁共振波谱分析。随后，处死所有动物，并对它们的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较高的表现受​​损率，包括三室社会测试、被动回避学习分析、旷场测试、旋转测试和新奇诱导的培养行为，表明自闭症症状。暴露于刺突蛋白（男性）会诱导海马和小脑 CA1-CA3 区域的神经胶质增生和神经元细胞死亡。暴露于刺突蛋白的雄性大鼠的丙二醛 (MDA)、肿瘤坏死因子 α (TNF-α)、白细胞介素 17 (IL-17)、核因子 κ B (NF-κB) 和乳酸水平显着升高，并且乳酸水平较低。脑源性神经营养因子（BDNF）水平高于对照组。我们的研究表明，产前接触 COVID-19 刺突蛋白与自闭症谱系障碍 (ASD) 等神经发育问题之间存在潜在关联。这些发现凸显了进一步研究 COVID-19 病毒对胚胎和胎儿发育的潜在影响以及对神经发育的潜在长期影响的重要性。

图形概要