• Neuroscience · Nov 2020

    Nogo-A/S1PR2 Signaling Pathway Inactivation Decreases Microvascular Damage and Enhances Microvascular Regeneration in PDMCI Mice.

    • Hongmei Tang, Yunxian Xu, Liru Liu, Lu He, Jingyu Huang, Jing Pan, Wenjie He, Yuxin Wang, Xubo Yang, Xiaohui Hou, and Kaishou Xu.
    • Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China.
    • Neuroscience. 2020 Nov 21; 449: 21-34.

    AbstractThe incidence of mild cognitive impairment in Parkinson's disease (PDMCI) is as high as 18-55%. However, the pathological mechanism of PDMCI is not yet clear. Our previous research showed that microvascular pathology and chronic cerebral hypoperfusion participated in the occurrence and development of PDMCI. Nogo-A has been suggested to be a negative regulator of microvascular regeneration in the central nervous system. Moreover, few insights have illuminated the mechanisms of Nogo-A and microvascular pathology in PDMCI. Therefore, we hypothesized that Nogo-A might be involved in the negative regulation of PDMCI angiogenesis. In this study, C57BL/6J mice were injected with Nogo-A-specific short hairpin RNA (shRNA-Nogo-A) in the lateral ventricle and intraperitoneally injected with a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid. Subjects were classified into the following five groups for the Morris water maze test: control (CON), CON + shRNA-GFP, CON + shRNA-Nogo-A, PDMCI, and PDMCI + shRNA-Nogo-A. Furthermore, blood-brain barrier (BBB) permeability, fluorescein isothiocyanate (FITC)-conjugated dextran, transmission electron microscopy (TEM), immunofluorescence and Western blot analyses were performed. The results showed that MPTP could cause spatial memory and behavioral impairment, significant microvascular impairment and increased Nogo-A expression. When Nogo-A expression was downregulated, the cognitive and microvascular impairments were alleviated, and the expression of sphingosine-1-phosphate receptor 2 (S1PR2) and the RhoA/ROCK signaling pathway were inhibited. These findings suggested that Nogo-A could bind to S1PR2, activate related signaling pathways, and lead to the inhibition of vascular remodeling in PDMCI mice. This study indicated that Nogo-A downregulation could mediate microvascular remodeling and provide further insights into the pathogenesis of PDMCI.Copyright © 2020 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…