NRG1–ErbB4 signaling promotes functional recovery in a murine model of traumatic brain injury via regulation of GABA release
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.
KeywordsNRG1–ErbB4 signaling Traumatic brain injury Neuroprotection GABA
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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Conflict of interest
The authors declare no financial conflict of interest regarding the publication of this article.
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