title: Downregulation of STIM2 improves neuronal survival after traumatic brain injury by alleviating calcium overload and mitochondrial dysfunction.
abstract: Although store-operated calcium entry (SOCE) has been implicated in several neurological disorders, the exact mechanism for its role in traumatic brain injury (TBI) has not been elucidated. In this study, we found that TBI upregulated the expression of a calcium sensor protein called stromal interactive molecule 2 (STIM2); however, the levels of its homologue, STIM1, were unaffected. Both STIM1 and STIM2 are crucial components of SOCE, both in vivo and in vitro. Using shRNA, we discovered that downregulation of STIM2, but not STIM1, significantly improved neuronal survival in both an in vitro and in vivo model of TBI, decreasing neuronal apoptosis, and preserving neurological function. This neuroprotection was associated with alleviating TBI-induced calcium overload and preserving mitochondrial function. Additionally, downregulation of STIM2 not only inhibited Ca(2+) release from the endoplasmic reticulum (ER), but also reduced SOCE-mediated Ca(2+) influx, decreased mitochondrial Ca(2+), restored mitochondrial morphology and improved mitochondrial function, including MMP maintenance, ROS production and ATP synthesis. These results indicate that inhibition of STIM2 can protect neurons from TBI by inhibiting calcium overload and preserving mitochondrial function. This suggests that STIM2 might be an effective interventional target for TBI.
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Wei
authors: W
authors: Rao
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Cheng
authors: C
authors: Peng
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Hao
authors: H
authors: Hui
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Kai
authors: K
authors: Wang
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Ning
authors: N
authors: Su
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Li
authors: L
authors: Wang
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Shu-Hui
authors: SH
authors: Dai
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Yue-Fan
authors: YF
authors: Yang
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Tao
authors: T
authors: Chen
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors: Peng
authors: P
authors: Luo
authors: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: feizhou@fmmu.edu.cn.
authors: Zhou
authors: Z
authors: Fei
keywords: Calcium homeostasis; Mitochondria dysfunction; Neurons; SOCE; Traumatic brain injury