TY - JOUR
T1 - Microglial depletion aggravates the severity of acute and chronic seizures in mice
AU - Wu, Wenning
AU - Li, Yujiao
AU - Wei, Yujia
AU - Bosco, Dale B.
AU - Xie, Manling
AU - Zhao, Ming Gao
AU - Richardson, Jason R.
AU - Wu, Long Jun
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/10
Y1 - 2020/10
N2 - Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1CreER/+:R26iDTA/+, CX3CR1CreER/+:R26iDTR/+, and CX3CR1CreER/+:Csf1rFlox/Flox mice. We found that microglial depletion led to worse kainic acid (KA)-induced status epilepticus, higher mortality rate, and increased neuronal degeneration in the hippocampus. In KA-induced chronic spontaneous recurrent seizures, microglial depletion increased seizure frequency, interictal spiking, and seizure duration. Therefore, microglial depletion aggravates the severity of KA-induced acute and chronic seizures. Interestingly, microglial repopulation reversed the effects of depletion upon KA-induced status epilepticus. Our results demonstrate a beneficial role of microglia in suppressing both acute and chronic seizures, suggesting that microglia are a potential therapeutic target for the management of epilepsy.
AB - Microglia are the resident immune cells of the center nervous system and participate in various neurological diseases. Here we determined the function of microglia in epileptogenesis using microglial ablation approaches. Three different microglia-specific genetic tools were used, CX3CR1CreER/+:R26iDTA/+, CX3CR1CreER/+:R26iDTR/+, and CX3CR1CreER/+:Csf1rFlox/Flox mice. We found that microglial depletion led to worse kainic acid (KA)-induced status epilepticus, higher mortality rate, and increased neuronal degeneration in the hippocampus. In KA-induced chronic spontaneous recurrent seizures, microglial depletion increased seizure frequency, interictal spiking, and seizure duration. Therefore, microglial depletion aggravates the severity of KA-induced acute and chronic seizures. Interestingly, microglial repopulation reversed the effects of depletion upon KA-induced status epilepticus. Our results demonstrate a beneficial role of microglia in suppressing both acute and chronic seizures, suggesting that microglia are a potential therapeutic target for the management of epilepsy.
KW - Epilepsy
KW - Kainic acid
KW - Microglia
KW - Microglia depletion
KW - Microglia repopulation
KW - Neuronal degeneration
KW - Spontaneous recurrent seizures
KW - Status epilepticus
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UR - http://www.scopus.com/inward/citedby.url?scp=85087501351&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2020.06.028
DO - 10.1016/j.bbi.2020.06.028
M3 - Article
C2 - 32621847
AN - SCOPUS:85087501351
SN - 0889-1591
VL - 89
SP - 245
EP - 255
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -