Glyphosate-based herbicides (GBH) are the most widely used pesticides worldwide. Despite considerable progress in describing the neurotoxic potential of GBH, the harmful effects on brain cytoarchitecture and behavior are still unclear. Here, we addressed the developmental impact of GBH by exposing female mice to 250 or 500 mg/kg doses of GBH during both pregnancy and lactation and then examined the downstream effects at the behavioral, neurochemical and molecular levels. We show that pre- and neonatal exposure to GBH impairs fertility and reproduction parameters as well as maternal behavior of exposed mothers. In offspring, GBH was responsible for a global delay in innate reflexes and a deficit in motor development. At the adult age, exposed animals showed a decrease of locomotor activity, sociability, learning and short- and long-term memory associated with alterations of cholinergic and dopaminergic systems. Furthermore, GBH-activated microglia and astrocytes, sign of neuroinflammation event in the medial prefrontal cortex and hippocampus. At the molecular level, a down-regulation of brain-derived neurotrophic factor (BDNF) expression and an up-regulation of tyrosine-related kinase receptor (TrkB), NR1 subunit of NMDA receptor as well as tumor necrosis factor α (TNFα) were found in the brain of GBH-exposed mice. The present work demonstrates that GBH induces numerous behavioral and cognitive abnormalities closely associated with significant histological, neurochemical and molecular impairments. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during developmental periods of central nervous system.

中文翻译：

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产前和产后接触草甘膦除草剂会导致成年小鼠的行为和认知障碍：皮质和海马功能障碍的证据。


草甘膦除草剂 (GBH) 是全球使用最广泛的农药。尽管在描述 GBH 的潜在神经毒性方面取得了相当大的进展，但对脑细胞结构和行为的有害影响仍不清楚。在这里，我们通过在怀孕和哺乳期间将雌性小鼠暴露于 250 或 500 mg/kg 剂量的 GBH 来研究 GBH 对发育的影响，然后检查行为、神经化学和分子水平的下游影响。我们发现，产前和新生儿接触 GBH 会损害生育力和生殖参数以及接触过的母亲的母亲行为。在后代中，GBH 导致先天反射的整体延迟和运动发育的缺陷。在成年时，暴露的动物表现出与胆碱能和多巴胺能系统改变相关的运动活动、社交能力、学习能力以及短期和长期记忆的下降。此外，GBH 激活的小胶质细胞和星形胶质细胞是内侧前额皮质和海马神经炎症事件的标志。在分子水平上，脑源性神经营养因子（BDNF）表达下调，酪氨酸相关激酶受体（TrkB）、NMDA受体NR1亚基以及肿瘤坏死因子α（TNFα）表达上调。在暴露于 GBH 的小鼠大脑中发现。目前的工作表明，GBH 会诱发许多与显着的组织学、神经化学和分子损伤密切相关的行为和认知异常。它还引发了人们对当前安全测试评估中枢神经系统发育期间接触农药风险的能力的根本担忧。