» Articles » PMID: 19903519

Microglial MyD88 Signaling Regulates Acute Neuronal Toxicity of LPS-stimulated Microglia in Vitro

Overview
Publisher Elsevier
Date 2009 Nov 12
PMID 19903519
Citations 38
Authors
Affiliations
Soon will be listed here.
Abstract

Although the role of microglial activation in neural injury remains controversial, there is increasing evidence for a detrimental effect in the immature brain, which may occur in response to release of neurotoxic substances including pro-inflammatory cytokines. However, the signaling mechanisms involved in microglial-induced neuronal cell death are unclear. Microglia isolated from the brains of wild-type (WT) or MyD88 knockout (KO) mice were exposed to PBS or the TLR4-ligand LPS (100 ng/mL) for 2, 6, 14, or 24 h, and the microglia-conditioned medium (MCM) collected. Detection of multiple inflammatory molecules in MCM was performed using a mouse 22-plex cytokine microbead array kit. Primary neuronal cultures were supplemented with the 14 or 24 h MCM, and the degree of neuronal apoptosis examined after exposure for 24 h. Results showed a rapid and sustained elevation in multiple inflammatory mediators in the MCM of WT microglia exposed to LPS, which was largely inhibited in MyD88 KO microglia. There was a significant increase in apoptotic death measured at 24 h in cultured neurons exposed to CM from either 14 or 24 h LPS-stimulated WT microglia (p<.05 vs. WT control). By contrast, there was no increase in apoptotic death in cultured neurons exposed to CM from 14 or 24 h LPS-stimulated MyD88 KO microglia (p=.15 vs. MyD88 KO control). These data suggest that MyD88-dependent activation of microglia by LPS causes release of factors directly toxic to neurons.

Citing Articles

Evaluation of the Efficacy of a Full-Spectrum Low-THC Plant Extract Using In Vitro Models of Inflammation and Excitotoxicity.

Ross-Munro E, Isikgel E, Fleiss B Biomolecules. 2024; 14(11).

PMID: 39595610 PMC: 11592195. DOI: 10.3390/biom14111434.


Key roles of glial cells in the encephalopathy of prematurity.

Steenwinckel J, Bokobza C, Laforge M, Shearer I, Miron V, Rua R Glia. 2023; 72(3):475-503.

PMID: 37909340 PMC: 10952406. DOI: 10.1002/glia.24474.


Paeonol regulates NLRP3 inflammasomes and pyroptosis to alleviate spinal cord injury of rat.

Zhao H, Wang X, Liu S, Zhang Q BMC Neurosci. 2022; 23(1):16.

PMID: 35303801 PMC: 8932340. DOI: 10.1186/s12868-022-00698-9.


The Impact of Systemic Inflammation on Alzheimer's Disease Pathology.

Xie J, Van Hoecke L, Vandenbroucke R Front Immunol. 2022; 12:796867.

PMID: 35069578 PMC: 8770958. DOI: 10.3389/fimmu.2021.796867.


Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia.

Madhi I, Kim J, Shin J, Kim Y Mol Med Rep. 2021; 24(4).

PMID: 34368872 PMC: 8365412. DOI: 10.3892/mmr.2021.12337.