Down-regulation of Neuregulin۲ (NRG۲) following spinal cord injury in C۵۷BL/۶ mice: Its implications in therapeutic potential

Objective(s): This study aims to elucidate the alterations in Neuregulin ۲ (NRG۲) and its receptor ErbB۴ following spinal cord injury (SCI), as well as to investigate the neuroprotective mechanisms of NRG۲ in neurons. Materials and Methods: Dataset GSE۹۳۵۶۱ was analyzed to verify the changes of NRG۲-ErbB۴ signaling pathway in mice following SCI. The levels of Iba-۱ and NRG۲ were analyzed by immunohistochemistry, and NRG۲ and pErbB۴ protein levels were detected by western blot. HT۲۲ cells were scratched and treated with NRG۲ dosed from ۰–۵ nM. Cell mobility was measured at the time point of ۰, ۲۴, and ۴۸ hr after scratch. Additionally, western blot was used to detect the protein levels of pErbB۴ and pAkt۱ at ۴۸ hr. Results: By analyzing dataset GSE۹۳۵۶۱, NRG۱, NRG۲, and NRG۳ were found to be decreased to different degrees post-SCI in mice. The results of immunohistochemistry showed that the level of Iba-۱ in the injured core area was significantly increased ۸ weeks post-SCI. Western blot analysis showed that the protein levels of NRG۲ and pErbB۴ were decreased significantly post-SCI. NRG۲ promoted HT۲۲ cell migration and dose-dependently increased pErbB۴ and pAkt۱ protein levels at doses ranging from ۰-۵ nM. Conclusion: The NRG۲-ErbB۴ signaling pathway was inhibited after SCI in mice. NRG۲ promotes the healing of HT۲۲ cells after scratch injury, and the mechanism of NRG۲ in the treatment of SCI may be ascribed to the activation of PI۳K-Akt signaling pathways downstream to NRG۲.

کلیدواژه ها:

C۵۷BL/۶ mouse ، Migration ، Nerve regeneration ، NRG۲ ، PI۳K-Akt ، Spinal cord injury (SCI)