Enhanced store-operated calcium entry (SOCE) exacerbates motor neurons apoptosis following spinal cord injury.

Spinal cord injury is pathologically characterized by the loss of motor function caused by neurons apoptosis. Store-operated calcium entry (SOCE) is widely known to dictate the apoptosis of various cell types. To examine SOCE in spinal cord injury and explore the role of SOCE in apoptosis, patients with spinal cord injury (SCI) and SCI mouse models were included. Expression of SOCE components and apoptosis-related proteins were examined by Western blotting. Calcium imaging was used to assess SOCE activity. As a result, we confirmed the enhanced levels of ORAI1 and STIM1 in SCI patients and SCI mouse models. In vitro study, tunicamycin impaired the viability of VSC4.1 cells (motoneuron-neuroblastoma hybrid cell line) and increased SOCE activity, the effects of which could be abolished by 2-APB. Furthermore, tunicamycinreduced BCL-2/BAX ratio was also reversed by 2-APB. Additionally, EdU assay and DCFH-DA staining confirmed the regulatory role of 2-APB in proliferation and ROS production. Of note is the improved hindlimb motor function and alleviated depression by 2-APB administration. Therefore, we conclude that SOCE may contribute to the pathogenesis of SCI by exacerbating the apoptosis of motoneurons.