Neuron-specific mitochondrial oxidative stress results in epilepsy, glucose dysregulation and a striking astrocyte response.
Neuron-specific mitochondrial oxidative stress results in epilepsy, glucose dysregulation and a striking astrocyte response.
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DOI：
10.1016/j.nbd.2021.105470
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发表时间：
2021-10
影响因子：
6.1
通讯作者：
Patel MN
中科院分区：
文献类型：
--
作者：
Fulton RE;Pearson-Smith JN;Huynh CQ;Fabisiak T;Liang LP;Aivazidis S;High BA;Buscaglia G;Corrigan T;Valdez R;Shimizu T;Patel MN
Mitochondrial superoxide (O2.−) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O2.− to these phenomena is unclear. Here, we selectively deleted superoxide dismutase-2 (SOD2) in neuronal basic helix-loop-helix transcription factor (NEX)-expressing cells restricting deletion to a subset of excitatory principle neurons primarily in the forebrain (cortex and hippocampus). This resulted in nSOD2 KO mice that lived into adulthood (2-3 months) with epilepsy, selective loss of neurons, metabolic rewiring and a marked mitohormetic gene response. Surprisingly, expression of an astrocytic gene, glial fibrillary acidic protein (GFAP) was significantly increased relative to WT. Further studies in rat primary neuron-glial cultures showed that increased mitochondrial O2.−, specifically in neurons, was sufficient to upregulate GFAP. These results suggest that neuron-specific mitochondrial O2.− is sufficient to drive a complex and catastrophic epileptic phenotype and highlights the ability of SOD2 to act in a cell-nonautonomous manner to influence an astrocytic response.
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影响因子：
9.3
作者：
Huang WY;Lin S;Chen HY;Chen YP;Chen TY;Hsu KS;Wu HM
通讯作者：
Wu HM
影响因子：
14.5
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影响因子：
5.5
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Dikalov, S
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Bailey DM
影响因子：
2.9
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Fujikawa, DG
通讯作者：
Fujikawa, DG