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The Role of Microglia in Epilepsy

小胶质细胞在癫痫中的作用

基本信息

批准号：
10576303
负责人：
Long-Jun Wu
金额：
$ 39.28万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2025-02-28
项目状态：
未结题

项目摘要

SUMMARY Our initial grant funding focused on the earliest period following experimentally-induced seizures. We documented robust physical interactions between microglia and neurons in epileptic contexts and concluded that microglia provide beneficial functions in the acute seizures. In this renewal, we will further investigate microglial activities in the epileptic brain in vivo and combine cellular and functional imaging with electrophysiological and behavioral studies in experimental mouse seizure models. We will extend our findings from the initial funding cycle to further characterize microglial activities in the epileptic brain following seizures and provide further evidence of microglial neuroprotection in the acute phase of kainic acid (KA)-induced seizures. In addition, we will investigate microglial roles in the epileptic brain in the chronic phase of epilepsy using microglial ablation and chemogenetic DREADD approaches. Our central hypothesis is that microglia play opposing roles during the acute phase of seizures and the chronic phase of epileptogenesis. This hypothesis will be tested along the following specific aims: In Aim 1, we will investigate the dynamics and function of seizure-induced microglial process pouches. In Aim 2, we will determine microglial contributions to epileptogenesis. Finally, in Aim 3, we will ascertain opposing microglial roles in acute seizures and chronic epilepsy using DREADD approaches. When completed, this grant will extend the findings of the initial funding to elucidate the beneficial roles for microglia in the acute phase of seizures Furthermore, this renewal will highlight detrimental contributions by microglia in promoting seizure-induced neurogenesis, neuronal sprouting, neuronal excitability and spontaneous seizures in the chronic phase of seizures. This study will not only improve our understanding of microglial mechanism to epileptogenesis but also demonstrate that microglia are potential therapeutic targets for the treatment seizures and epilepsy.

总结

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling.

DOI：
10.1038/s41593-019-0511-3
发表时间：
2019-11-01
期刊：
Nature neuroscience
影响因子：
25
作者：
Liu, Yong U;Ying, Yanlu;Wu, Long-Jun
通讯作者：
Wu, Long-Jun

Microglial voltage-gated proton channel Hv1 in spinal cord injury.

DOI：
10.4103/1673-5374.327325
发表时间：
2022-06
期刊：
Neural regeneration research
影响因子：
6.1
作者：
Zheng J;Murugan M;Wang L;Wu LJ
通讯作者：
Wu LJ

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

局部质子瞬变激活酸敏感离子通道揭示了它们在质子信号传导中的作用

DOI：
10.1038/srep14125
发表时间：
2015-09-15
期刊：
Scientific reports
影响因子：
4.6
作者：
Zeng WZ;Liu DS;Liu L;She L;Wu LJ;Xu TL
通讯作者：
Xu TL

Neuroimmune interaction in seizures and epilepsy: focusing on monocyte infiltration.

DOI：
10.1111/febs.15428
发表时间：
2020-11
期刊：
The FEBS journal
影响因子：
0
作者：
Bosco DB;Tian DS;Wu LJ
通讯作者：
Wu LJ

Optogenetic activation of spinal microglia triggers chronic pain in mice.

DOI：
10.1371/journal.pbio.3001154
发表时间：
2021-03
期刊：
PLoS biology
影响因子：
9.8
作者：
Yi MH;Liu YU;Umpierre AD;Chen T;Ying Y;Zheng J;Dheer A;Bosco DB;Dong H;Wu LJ
通讯作者：
Wu LJ