1,4-butanediol (1,4-BD) is a known γ-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose–effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-α) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.

1,4-丁二醇 (1,4-BD) 是一种已知的 γ-羟基丁酸 (GHB) 前体，摄入后会影响神经系统，导致无法控制的行为后果。在本研究中，我们研究了 1,4-BD 是否在 PC12 细胞中诱导氧化应激和炎症，并评估了 1,4-BD 与学习和记忆相关的毒性作用。CCK-8 结果显示，当作用持续时间为 2 小时或 4 小时时，PC12 细胞的细胞活力与 1,4-BD 之间存在剂量效应关系。检测试剂盒结果显示，1,4-BD 降低了谷胱甘肽 (GSH)、谷胱甘肽过氧化物酶 (GSH-px)、超氧化物歧化酶 (SOD)、乙酰胆碱 (Ach) 的水平，并增加了丙二醛 (MDA)、一氧化氮 ( NO) 和乙酰胆碱酯酶 (AchE)。Elisa 试剂盒结果表明 1,4-BD 降低了突触素 I (SYN-1) 的水平，突触后密度蛋白 95 (PSD-95)、生长相关蛋白 43 (GAP-43) 并增加肿瘤坏死因子 α (TNF-α) 和白细胞介素 6 (IL-6) 的水平。RT-PCR结果显示PSD-95、SYN-1和GAP-43的mRNA水平显着降低。PC12细胞中磷酸化细胞外信号调节蛋白激酶1/2（p-ERK1/2）、磷酸化cAMP反应元件结合蛋白（p-CREB）和脑源性神经营养因子（BDNF）蛋白的表达显着降低。印迹。总体而言，这些结果表明 1,4-BD 可能通过 ERK1/2-CREB-BDNF 通路影响突触可塑性，导致 Ach 释放减少并最终导致学习和记忆障碍。此外，1,4-BD 诱导的氧化应激和炎症也可能导致学习和记忆障碍。