During the mammalian brain development, oligodendrocyte progenitor cells (OPCs) are generated from neuroepithelium and migrate throughout the brain. Myelination is a tightly regulated process which involves time framed sequential events of OPCs proliferation, migration, differentiation and interaction with axons for functional insulated sheath formation. Myelin is essential for efficient and rapid conduction of electric impulses and its loss in the hippocampus of the brain may result in impaired memory and long-term neurological deficits. Carbofuran, a carbamate pesticide is known to cause inhibition of hippocampal neurogenesis and memory dysfunctions in rats. Nonetheless, the effects of carbofuran on OPCs proliferation, fate determination, maturation/differentiation and myelination potential in the hippocampus of the rat brain are still completely elusive. Herein, we investigated the effects of sub-chronic exposure of carbofuran during two different time periods including prenatal and adult brain development in rats. We observed carbofuran hampers OPCs proliferation (BrdU incorporation) and oligodendroglial differentiation in vitro. Similar effects of carbofuran were also observed in the hippocampus region of the brain at both the time points. Carbofuran exposure resulted in reduced expression of key genes and proteins involved in the regulation of oligodendrocyte development and functional myelination. It also affects the survival of oligodendrocytes by inducing apoptotic cell death. The ultrastructural analysis of myelin architecture clearly depicted carbofuran-mediated negative effects on myelin compaction and g-ratio alteration. Conclusively, our study demonstrated that carbofuran alters myelination potential in the hippocampus, which leads to cognitive deficits in rats.

在哺乳动物的大脑发育过程中，少突胶质细胞祖细胞（OPC）从神经上皮细胞生成，并在整个大脑中迁移。髓鞘形成是一个严格调控的过程，涉及OPC增殖，迁移，分化和与轴突相互作用的时间框架顺序事件，以形成功能性绝缘鞘。髓磷脂对于有效快速地传导电脉冲至关重要，其在大脑海马体中的丢失可能导致记忆力减退和长期神经功能缺损。已知氨基甲酸酯类杀虫剂呋喃丹能抑制大鼠海马神经发生和记忆功能障碍。但是，呋喃丹对OPC增殖，命运决定，大鼠大脑海马的成熟/分化和髓鞘化潜能仍然完全难以捉摸。在这里，我们调查了在包括产前和成年大鼠大脑发育在内的两个不同时间段，亚呋喃呋喃亚慢性暴露的影响。我们观察到了体外呋喃呋喃阻碍OPCs增殖（BrdU掺入）和少突胶质细胞分化。在两个时间点的大脑海马区也观察到了呋喃丹的类似作用。暴露于呋喃丹会导致参与少突胶质细胞发育和功能性髓鞘形成的调节的关键基因和蛋白质的表达减少。它还通过诱导凋亡性细胞死亡来影响少突胶质细胞的存活。髓鞘结构的超微结构分析清楚地表明了呋喃丹介导的对髓鞘紧实和g值变化的负面影响。最终，我们的研究表明，呋喃丹会改变海马体的髓鞘形成潜能，从而导致大鼠认知功能障碍。