Abstract：
Cannabis use is a worldwide issue with the development of legalization. Prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, is related to affect fetal nervous system development. In our present study, we administered THC to pregnant mice from gestational day 5.5-12.5. Differences in neuronal cell composition and organization between the two groups were found by staining sections of the offspring hippocampus at PND21. In addition, RNA-seq of hippocampal tissue also suggested differences in gene expression due to THC treatment, especially significant enrichment to neurogenesis and neural differentiation. Subsequently, the effect of THC treatment on the proliferation and differentiation capacity of neural stem cells (NSCs) was confirmed. Based on the RNA-seq results, we selected the differentially expressed transcription factor MEF2C for validation. The effect of THC treatment on NSCs differentiation was found to be regulated by knocking down the expression of MEF2C in NSCs. Considering that THC is an agonist of cannabinoid receptor (CB1R), the differentiation outcome of NSC after THC treatment was significantly rescued, by pretreating with the CB1R inhibitor Rimonabant. Notably, pretreatment with Rimonabant restored the expression of MEF2C. Taken together, the present results suggested that THC regulated the MEF2C pathway through CB1R and had an impact on hippocampal neurodevelopment.
摘要：
随着合法化的发展，大麻的使用是一个世界性的问题。产前暴露于Δ9-四氢大麻酚（THC），大麻的主要精神活性成分，与影响胎儿神经系统发育有关。在我们目前的研究中，我们从妊娠第5.5天到12.5天对妊娠小鼠施用THC。通过在PND21处的后代海马的染色切片发现两组之间的神经元细胞组成和组织的差异。此外,海马组织的RNA-seq也提示了由于THC治疗的基因表达差异，特别是对神经发生和神经分化的显著富集。随后，证实了THC处理对神经干细胞（NSCs）增殖和分化能力的影响。根据RNA-seq结果,我们选择差异表达的转录因子MEF2C进行验证.发现THC处理对NSCs分化的影响通过敲低NSCs中MEF2C的表达来调节。考虑到THC是大麻素受体（CB1R）的激动剂，THC治疗后NSC的分化结果显着挽救，通过用CB1R抑制剂利莫那班预处理。值得注意的是,利莫那班预处理可恢复MEF2C的表达。一起来看,本研究结果提示THC通过CB1R调节MEF2C通路,影响海马神经发育。
