Neonatal sepsis is associated with cognitive deficit in the later life. Axonal myelination plays a pivotal role in neurotransmission and formation of learning and memory. This study aimed to explore if systemic lipopolysaccharide (LPS) injection would induce hypomyelination in the prefrontal cortex and hippocampus in developing septic neonatal rats. Sprague–Dawley rats (1-day old) were injected with LPS (1 mg/kg) intraperitoneally. By electron microscopy, axonal hypomyelination was evident in the subcortical white matter and hippocampus. The expression of myelin proteins including CNPase, MBP, PLP and MAG was downregulated in both areas of the brain at 7, 14 and 28 days after LPS injection. The frequency of MBP and PLP-positive oligodendrocyte was significantly reduced using in situ hybridization in the cerebral cortex and hippocampus at the corresponding time points after LPS injection, whereas the expression of NG2 and PDGFRα was noticeably increased. In tandem with this was reduction of Olig1 and Olig2 expressions which are involved in differentiation/maturation of OPCs. Expression of NFL, NFM, and NFH was significantly downregulated, indicating that axon development was disrupted after LPS injection. Morris Water Maze behavioral test, Open field test, Rotarod test, and Pole test were used to evaluate neurological behaviors of 28 days rats. The rats in the LPS group showed the impairment of motor coordination, balance, memory, and learning ability and represented bradykinesia and anxiety-like behavior. The present results suggest that following systemic LPS injection, differentiation/maturation of OPCs was affected which may be attributed to the inhibition of transcription factors Olig1 and Olig2 expression resulting in impairment to axonal development. It is suggested that this would ultimately lead to axonal hypomyelination in the prefrontal cortex and hippocampus, which may be associated with neurological deficits in later life.

中文翻译：

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实验诱导的败血症导致新生大鼠前额叶皮层和海马广泛的髓鞘形成不足。

新生儿败血症与晚年的认知缺陷有关。轴突髓鞘形成在神经传递和学习记忆的形成中起着关键作用。本研究旨在探讨全身性脂多糖 (LPS) 注射是否会导致脓毒症新生大鼠前额叶皮层和海马的髓鞘形成不足。Sprague-Dawley 大鼠（1 日龄）腹膜内注射 LPS（1 毫克/千克）。通过电子显微镜，在皮质下白质和海马中轴突髓鞘形成明显减少。在注射 LPS 后 7、14 和 28 天，髓鞘蛋白（包括 CNPase、MBP、PLP 和 MAG）的表达在大脑的两个区域均下调。在注射LPS后的相应时间点，在大脑皮层和海马中使用原位杂交显着降低MBP和PLP阳性少突胶质细胞的频率，而NG2和PDGFRα的表达显着增加。与此相伴的是 Olig1 和 Olig2 表达的减少，这些表达与 OPCs 的分化/成熟有关。NFL、NFM 和 NFH 的表达显着下调，表明注射 LPS 后轴突发育受到干扰。采用Morris水迷宫行为试验、野外试验、Rotarod试验和极杆试验评价28天大鼠的神经行为。LPS组大鼠表现出运动协调、平衡、记忆和学习能力受损，表现出运动迟缓和焦虑样行为。目前的结果表明，在全身注射 LPS 后，OPCs 的分化/成熟受到影响，这可能是由于转录因子 Olig1 和 Olig2 表达的抑制导致轴突发育受损。有人提出，这最终会导致前额叶皮层和海马的轴突髓鞘形成不足，这可能与晚年的神经功能缺损有关。