| First Author | Fulton RE | Year | 2021 |
| Journal | Neurobiol Dis | Volume | 158 |
| Pages | 105470 | PubMed ID | 34371143 |
| Mgi Jnum | J:311397 | Mgi Id | MGI:6764096 |
| Doi | 10.1016/j.nbd.2021.105470 | Citation | Fulton RE, et al. (2021) Neuron-specific mitochondrial oxidative stress results in epilepsy, glucose dysregulation and a striking astrocyte response. Neurobiol Dis 158:105470 |
| abstractText | 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. |
