TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States

被引：55

作者：

Batti, Laura ^{[1
]}

Sundukova, Mayya ^{[1
]}

Murana, Emanuele ^{[4
,5
]}

Pimpinella, Sofia ^{[1
]}

Reis, Fernanda De Castro ^{[1
]}

Pagani, Francesca ^{[3
]}

Wang, Hong ^{[6
]}

Pellegrino, Eloisa ^{[4
,5
]}

Perlas, Emerald ^{[1
]}

Di Angelantonio, Silvia ^{[3
,4
,5
]}

Ragozzino, Davide ^{[4
,5
,7
]}

Heppenstall, Paul A. ^{[1
,2
]}

机构：

[1] EMBL, Mouse Biol Unit, Via Ramarini 32, I-00015 Monterotondo, Italy

[2] MMPU, D-69117 Heidelberg, Germany

[3] Ist Italiano Tecnol, Ctr Life Nanosci, Viale Regina Elena 291, I-00161 Rome, Italy

[4] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[5] Univ Roma La Sapienza, Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[6] Heidelberg Univ, Pharmacol Inst, Neuenheimer Feld 366, D-69120 Heidelberg, Germany

[7] IRCCS Neuromed, Via Atinese, I-86077 Pozzilli, Italy

来源：

CELL REPORTS | 2016年 / 15卷 / 12期

关键词：

PERIPHERAL-NERVE INJURY; SUPERFICIAL DORSAL-HORN; CHLORIDE CHANNEL; ANION GRADIENT; IMMUNE CELLS; CL-CHANNELS; ANOCTAMIN; MACROPHAGES; ACTIVATION; INHIBITION;

D O I：

10.1016/j.celrep.2016.05.039

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Neuropathic pain is a widespread chronic pain state that results from injury to the nervous system. Spinal microglia play a causative role in the pathogenesis of neuropathic pain through secretion of growth factors and cytokines. Here, we investigated the contribution of TMEM16F, a protein that functions as a Ca2+-dependent ion channel and a phospholipid scramblase, to microglial activity during neuropathic pain. We demonstrate that mice with a conditional ablation of TMEM16F in microglia do not develop mechanical hypersensitivity upon nerve injury. In the absence of TMEM16F, microglia display deficits in process motility and phagocytosis. Moreover, loss of GABA immunoreactivity upon injury is spared in TMEM16F conditional knockout mice. Collectively, these data indicate that TMEM16F is an essential component of the microglial response to injury and suggest the importance of microglial phagocytosis in the pathogenesis of neuropathic pain.

引用

页码：2608 / 2615

页数：8

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