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Sodium butyrate triggers a functional elongation of microglial process via Akt-small RhoGTPase activation and HDACs inhibition.

Abstract：

:Microglia, a type of immune cell in the brain, are in a ramified status with branched processes in normal conditions. Upon pathological stimulation, microglia retract their processes and become activated. Searching methods to make the activated microglia return to ramified status would help cope with injuries induced by neuroinflammation. Here, we investigated the influence of sodium butyrate (SB), a sodium salt form of butyrate produced by fermentation of dietary fibers in the gut on microglial process. Results showed that SB induced reversible elongations of microglial process in both normal and inflammatory conditions, and these elongations were accompanied with significant changes in markers reflecting the pro-inflammatory and anti-inflammatory status of microglia. The protein kinase B (Akt)-RhoGTPase signal was considered to mediate the effect of SB on microglial process, as: i) SB activated the small RhoGTPases Rac1 and Cdc42; ii) SB promotes Akt phosphorylation; iii) Rac1, Cdc42, and Akt inhibition abrogated the pro-elongation effect of SB on microglial process. Further analysis showed that incubation of microglia with two other histone deacetylases (HDACs) inhibitors trichostatin A (TSA) and valproic acid (VPA) also promoted microglial process elongation and Akt phosphorylation, suggesting that the SB-triggered microglial process elongation may be mediated by HDACs inhibition. Furthermore, Akt inhibition prevented the anti-inflammatory effect of SB in primary cultured microglia, and abrogated the inhibitory effects of SB on microglial process retraction and behavioral abnormalities induced by lipopolysaccharide (LPS). These results for the first time identify an anti-inflammatory role of SB from the aspect of microglial process elongation.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Wang P,Zhang Y,Gong Y,Yang R,Chen Z,Hu W,Wu Y,Gao M,Xu X,Qin Y,Huang C

doi

10.1016/j.nbd.2017.12.006

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

12-25

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(17)30284-X

journal_volume

111

pub_type

杂志文章

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