An increase in voltage-gated sodium channel current elicits microglial activation followed inflammatory responses in vitro and in vivo after spinal cord injury

Title
An increase in voltage-gated sodium channel current elicits microglial activation followed inflammatory responses in vitro and in vivo after spinal cord injury
Authors
정길영이지영임혜원오태환윤태영
Keywords
microglia; spinal cord injury; tetrodotoxin; voltage-gated sodium channels
Issue Date
2013-11
Publisher
GLIA
Citation
VOL 61, NO 11, 1807-1821
Abstract
Inflammation induced by microglial activation plays a pivotal role in progressive degeneration after traumatic spinal cord injury (SCI). Voltage-gated sodium channels (VGSCs) are also implicated in microglial activation following injury. However, direct evidence that VGSCs are involved in microglial activation after injury has not been demonstrated yet. Here, we show that the increase in VGSC inward current elicited microglial activation followed inflammatory responses, leading to cell death after injury in vitro and in vivo. Isoforms of sodium channel, Nav1.1, Nav1.2, and Nav1.6 were expressed in primary microglia, and the inward current of VGSC was increased by LPS treatment, which was blocked by a sodium channel blocker, tetrodotoxin (TTX). TTX inhibited LPS-induced NF-κB activation, expression of TNF-α, IL-1β and inducible nitric oxide synthase, and NO production. LPS-induced p38MAPK activation followed pro-nerve growth factor (proNGF) production was inhibited by TTX, whereas LPS-induced JNK activation was not. TTX also inhibited caspase-3 activation and cell death of primary cortical neurons in neuron/microglia co-cultures by inhibiting LPS-induced microglia activation. Furthermore, TTX attenuated caspase-3 activation and oligodendrocyte cell death at 5 d after SCI by inhibiting microglia activation and p38MAPK activation followed proNGF production, which is known to mediate oligodendrocyte cell death. Our study thus suggests that the increase in inward current of VGSC appears to be an early event required for microglia activation after injury.
URI
http://pubs.kist.re.kr/handle/201004/46659
ISSN
08941491
Appears in Collections:
KIST Publication > Article
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