Microglia activation mediated by toll-like receptor-4 impairs brain white matter tracts in rats

Xinglong Yang, Jingdong Zhang, Lian Duan, Huangui Xiong, Yanping Jiang, Houcheng Liang

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke. Axon degeneration and demyelination can activate microglia; however, it is unclear whether early microglia activation can impair the function of white matter tracts and lead to injury. Rat corpus callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS + Rhodobacter sphaeroides (RS)-LPS that is a toll-like receptor 4 (TLR-4) antagonist. Functional changes reflected by the change of axon compound action potentials (CAPs) and the accumulation of β-amyloid precursor protein (β-APP) in CC nerve fibers. Microglia activation was monitored by ionized calcium binding adaptor-1 immunofluorescent stain, based on well-established morphological criteria and paralleled proportional area measurement. Input-output (I/O) curves of CAPs in response to increased stimuli were significantly downshifted in a dose-dependent manner in LPS (0.2, 0.5 and 1.0 μg/mL)-treated slices, implying that axons neurophysiological function was undermined. LPS caused significant β-APP accumulation in CC tissues, reflecting the deterioration of fast axon transport. LPS-induced I/O curve downshift and β-APP accumulation were significantly reversed by the pre-treatment or co-incubation with RS-LPS. RS-LPS alone did not change the I/O curve. The degree of malfunction was correlated with microglia activation, as was shown by the measurements of proportional areas. Function of CC nerve fibers was evidently impaired by microglia activation and reversed by a TLP-4 antagonist, suggesting that the TLP-4 pathway lead to microglia activation.

Original languageEnglish (US)
Pages (from-to)136-144
Number of pages9
JournalJournal of Biomedical Research
Volume32
Issue number2
DOIs
Publication statusPublished - Jan 1 2018

    Fingerprint

Keywords

  • Lipopolysaccharide
  • Microglia activation
  • Rhodobacter sphaeroides
  • Toll-like receptor 4
  • White matter tract malfunction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this