Abstract
Traumatic brain injury (TBI) is a serious health problem in the world. However, little is known about the pathogenesis and molecular mechanisms of TBI. Here, we show that TBI activates neuregulin 1 (NRG1)-ErbB4 signaling, with an increased expression of NRG1 and ErbB4 in the traumatic region. Specifically knocking out ErbB4 in parvalbumin-positive (PV+) interneurons exacerbates motor function deficits in mice after TBI. Consistently, PV-ErbB4−/− mice showed larger necrotic area and more edema when compared with PV-ErbB4+/+ mice. Replenishment of NRG1 through intranasal application of the recombinant protein in PV-ErbB4+/+ mice enhanced neurological function. Moreover, using an in vitro neuronal culture system, we found that NRG1–ErbB4 signaling protects neurons from glutamate-induced death, and such protective effects could be diminished by GABA receptor antagonist. These results indicate that NRG-ErbB4 signaling protects cortical neurons from TBI-induced damage, and such effect is probably mediated by promoting GABA activity. Taken together, these findings unveil a previously unappreciated role for NRG1-ErB4 signaling in preventing neuronal cell death during functional recovery after TBI.
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Funding
This research was supported by the National Natural Science Foundation of China (31971035, 81471116, 31771182, 81560196), and the Natural Science Foundation of Jiangxi Province (20171ACB20002).
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Deng, W., Luo, F., Li, Bm. et al. NRG1–ErbB4 signaling promotes functional recovery in a murine model of traumatic brain injury via regulation of GABA release. Exp Brain Res 237, 3351–3362 (2019). https://doi.org/10.1007/s00221-019-05680-2
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DOI: https://doi.org/10.1007/s00221-019-05680-2