TLR1 expression in mouse brain was increased in a KA-induced seizure model

Wang, Faxiang; Liu, Shiyong; Zheng, Xin; Chen, Xin; Lu, Lin-Xiang; Cui, Bin; Xiong, Xiao‐Yi; Shu, Hai-Feng; Yang, Qingwu; Yang, Hui

doi:10.1007/s00011-015-0828-7

Cited by 22 publications

(18 citation statements)

References 35 publications

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“…In agreement with previous studies, KA injection (15 mg/kg, i.p.) induced epileptic seizures in this study [ 36 , 41 – 43 ]. SAHA pretreatment (10 or 50 mg/kg) reduced KA-induced neuronal apoptosis, suggesting SAHA as a potent neuroprotective and anticonvulsant agent.…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation

Mao

2016

BMC Neurosci

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BackgroundEpilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. Seizure-induced TLR4/MYD88 signaling plays a critical role in activating microglia and triggering neuron apoptosis. SAHA is a histone deacetylase inhibitor that regulates gene expression by increasing chromatin histone acetylation. In this study, we investigated the role of SAHA in TLR4/MYD88 signaling in a rat seizure model.ResultsSprague–Dawley rats with kainic acid (KA)-induced seizures were treated with SAHA. The expression of TLR4, MYD88, NF-κB P65 and IL-1β in hippocampus was detected at hour 2 and 6 and day 1, 2, and 3 post seizure. SAHA pretreatment increased seizure latency and decreased seizure scores. The expression levels of TLR4, MYD88, NF-κB and IL-1β increased significantly in both activated microglia and apoptotic neurons after KA treatment. The effects were attenuated by SAHA. Chromatin immunoprecipitation assays indicated that the H3 histone acetylation levels significantly decreased while H3K9 levels significantly increased in the KA treatment group. The H3 and H3K9 acetylation levels returned to control levels after SAHA (50 mg/kg) pretreatment. There was a positive correlation between the expression of TLR4 and the acetylation levels of H3K9.ConclusionsHistone deacetylase inhibitor SAHA can suppress seizure-induced TLR4/MYD88 signaling and inhibit TLR4 gene expression through histone acetylation regulation. This suggests that SAHA may protect against seizure-induced brain damage.

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Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation

Mao

2016

BMC Neurosci

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“…Different stimuli may lead to increased expression of microglia TLRs, such as hypoxia (Smith et al, 2013 ; Yao et al, 2013 ), LPS (Kielian et al, 2005 ; Yousif et al, 2018 ), Poly(I:C; Yousif et al, 2018 ), kainic acid (Wang et al, 2015 ; Hu and Mao, 2016 ), α-synuclein (Béraud et al, 2011 ; Daniele et al, 2015 ) and amyloid beta (Aβ; Jana et al, 2008 ; Richard et al, 2008 ; Caldeira et al, 2017 ).…”

Section: Tlr Expression In the Cnsmentioning

confidence: 99%

Role of Microglia TLRs in Neurodegeneration

Fiebich

Cra

et al. 2018

Front. Cell. Neurosci.

218

152

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Toll-like receptors (TLRs) are a group of receptors widely distributed in the organism. In the central nervous system, they are expressed in neurons, astrocytes and microglia. Although their involvement in immunity is notorious, different articles have demonstrated their roles in physiological and pathological conditions, including neurodegeneration. There is increasing evidence of an involvement of TLRs, especially TLR2, 4 and 9 in neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). In this sense, their expression in microglia might modulate the activity of these cells, which in turn, lead to protective or deleterious effects over neurons and other cells. Therefore, TLRs might mediate the link between inflammation and neurodegenerative diseases. However, further studies have to be performed to elucidate the role of the other TLRs in these diseases and to further prove and confirm the pathophysiological role of all TLRs in neurodegeneration. In this article, we revise and summarize the current knowledge regarding the role of TLRs in neurodegeneration with the focus on the possible functions of these receptors in microglia.

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“…Following injury, activation of these toll-like receptors can contribute to continued glutamate excitotoxicity out to several weeks [59]. Wang and colleagues showed that toll-like receptors are upregulated following kainic acid administration [60]. Specifically, toll-like receptor 4 is associated with temporal lobe seizures following trauma [61].…”

Section: Neuroinflammationmentioning

confidence: 99%

Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure

Lucke‐Wold

Nguyen

Turner

et al. 2015

Seizure

124

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Post-traumatic epilepsy continues to be a major concern for those experiencing traumatic brain injury. Post-traumatic epilepsy accounts for 10-20% of epilepsy cases in the general population. While seizure prophylaxis can prevent early onset seizures, no available treatments effectively prevent late-onset seizure. Little is known about the progression of neural injury over time and how this injury progression contributes to late onset seizure development. In this comprehensive review, we discuss the epidemiology and risk factors for post-traumatic epilepsy and the current pharmacologic agents used for treatment. We highlight limitations with the current approach and offer suggestions for remedying the knowledge gap. Critical to this pursuit is the design of pre-clinical models to investigate important mechanistic factors responsible for post-traumatic epilepsy development. We discuss what the current models have provided in terms of understanding acute injury and what is needed to advance understanding regarding late onset seizure. New model designs will be used to investigate novel pathways linking acute injury to chronic changes within the brain. Important components of this transition are likely mediated by toll-like receptors, neuroinflammation, and tauopathy. In the final section, we highlight current experimental therapies that may prove promising in preventing and treating post-traumatic epilepsy. By increasing understanding about post-traumatic epilepsy and injury expansion over time, it will be possible to design better treatments with specific molecular targets to prevent late-onset seizure occurrence following traumatic brain injury.

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TLR1 expression in mouse brain was increased in a KA-induced seizure model

Abstract: These results demonstrate that cortical and hippocampal sub-regional expression of TLR1 is altered during epileptogenesis in a time- and location-specific manner, suggesting a close association with the process of epilepsy.

Cited by 22 publications

References 35 publications

Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation

Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation

Role of Microglia TLRs in Neurodegeneration

Traumatic brain injury and epilepsy: Underlying mechanisms leading to seizure

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