• Neuroscience · Dec 2019

    Postnatal lipopolysaccharide exposure impairs adult neurogenesis and causes depression-like behaviors through astrocytes activation triggering GABAA receptor downregulation.

    • Min Liang, Haiquan Zhong, Jing Rong, Yingchun Li, Chunting Zhu, Li Zhou, and Rong Zhou.
    • Department of Physiology, Nanjing Medical University, Jiangsu, China.
    • Neuroscience. 2019 Dec 1; 422: 21-31.

    AbstractGrowing evidence indicates that early-life inflammation has adverse effects on adult hippocampal neurogenesis and GABA system. Based the report that hippocampal GABA system is a key modulator in adult hippocampal neurogenesis, the aim of this study was to investigate whether and how early inflammation affects GABAergic system resulting in the alterations of adult hippocampal neurogenesis and related behaviors. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days (PND) 3-5. Behavioral tests were used to explore LPS-induced depression-like behaviors of adult mice. Immunohistochemistry staining and western blot were employed to detect adult neurogenesis, GABAergic system, glia activation and BDNF-TrkB pathway in the hippocampus. LPS-treated mice developed a depression phenotype with the inhibited maturation of hippocampal newborn neurons in adulthood. Compared with controls, LPS mice showed a decreased expression of GABAA receptor (GABAAR) protein. GABAAR agonist phenobarbital could rectify the decrease of BrdU+/NeuN+ cells in LPS mice. Additionally, postnatal LPS treatment resulted in the activation of astrocytes and the increase expression of toll-like receptor 4 (TLR4) in the second postnatal week and the downregulation of BDNF-TrkB pathway in adulthood. The treatment with TLR4 inhibitor TAK-242 restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in LPS mice via improving GABAAR. The results indicate that postnatal LPS exposure impairs adult hippocampal neurogenesis and causes depression-like behaviors through early astrocytes activation triggering the later GABAAR downregulation.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…