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01-09-2020 | Septicemia | Original Paper

Experimentally Induced Sepsis Causes Extensive Hypomyelination in the Prefrontal Cortex and Hippocampus in Neonatal Rats

Authors: Peixian Huang, Xuan Chen, Xiaoli Hu, Qiuping Zhou, Lanfen Lin, Shuqi Jiang, Hui Fu, Yajie Xiong, Hongke Zeng, Ming Fang, Chunbo Chen, Yiyu Deng

Published in: NeuroMolecular Medicine | Issue 3/2020

Abstract

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.

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Title: Experimentally Induced Sepsis Causes Extensive Hypomyelination in the Prefrontal Cortex and Hippocampus in Neonatal Rats
Authors: Peixian Huang
Xuan Chen
Xiaoli Hu
Qiuping Zhou
Lanfen Lin
Shuqi Jiang
Hui Fu
Yajie Xiong
Hongke Zeng
Ming Fang
Chunbo Chen
Yiyu Deng
Publication date: 01-09-2020
Publisher: Springer US
Keywords: Septicemia
Septicemia
Published in: NeuroMolecular Medicine / Issue 3/2020
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-020-08602-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Experimentally Induced Sepsis Causes Extensive Hypomyelination in the Prefrontal Cortex and Hippocampus in Neonatal Rats

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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