Journal
EXPERIMENTAL NEUROLOGY
Volume 345, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2021.113818
Keywords
Transcranial direct-current stimulation; Ischemic stroke; Cerebral ischemia-reperfusion injury; Cezanne; SIRT6; DNA DSB
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Funding
- National Key R&D Program of China [2019YFC0120000, 2018YFC1312300]
- National Natural Science Foundation of China [NSFC: 82071385]
- Key Research and Development Project of Shandong [2019JZZY021010]
- Fundamental Research Funds for the Central Universities [2042020kf0090]
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The study found that tDCS treatment can reduce infarct volume after rat cerebral ischemia-reperfusion injury and improve the function of stroke animals. It was revealed that tDCS suppresses the upregulation of Cezanne, increases the level of SIRT6, and reduces DNA double-strand breaks, ultimately exerting neuroprotective effects in ischemic neurons.
Transcranial direct-current stimulation (tDCS) is proved safe and shows therapeutic effect in cerebral ischemic stroke in clinical trials. But the underlying molecular mechanisms remain unclear. Here we show that tDCS treatment reduces the infarct volume after rat cerebral ischemia-reperfusion (I/R) injury and results in functional improvement of stroke animals. At the cellular and molecular level, tDCS suppresses I/R-induced upregulation of Cezanne in the ischemic neurons. Cezanne inhibition confers neuroprotection after rat I/R and oxygen glucose deprivation (OGD) in the cortical neuronal cultures. Inhibiting Cezanne increases the level of SIRT6 that is downregulated in the ischemic neurons. Suppressing SIRT6 blocks Cezanne inhibition-induced neuroprotective effect and overexpressing SIRT6 attenuates OGD-induced neuronal death. We further show that downregulating Cezanne reduces DNA double-strand break (DSB) through upregulation of SIRT6 in OGD-insulted neurons. Together, this study suggests that Cezanne-dependent SIRT6-DNA DSB signaling pathway may mediate the neuroprotective effect of tDCS in ischemic neurons.
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