TY - JOUR
T1 - Microglia activation mediated by toll-like receptor-4 impairs brain white matter tracts in rats
AU - Yang, Xinglong
AU - Zhang, Jingdong
AU - Duan, Lian
AU - Xiong, Huangui
AU - Jiang, Yanping
AU - Liang, Houcheng
N1 - Publisher Copyright:
© 2018 by the Journal of Biomedical Research.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Lipopolysaccharide
KW - Microglia activation
KW - Rhodobacter sphaeroides
KW - Toll-like receptor 4
KW - White matter tract malfunction
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U2 - 10.7555/JBR.32.20170033
DO - 10.7555/JBR.32.20170033
M3 - Article
C2 - 29358565
AN - SCOPUS:85053167384
SN - 1674-8301
VL - 32
SP - 136
EP - 144
JO - Journal of Biomedical Research
JF - Journal of Biomedical Research
IS - 2
ER -