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Knockdown of STIM1 Improves Neuronal Survival After Traumatic Neuronal Injury Through Regulating mGluR1-Dependent Ca2+ Signaling in Mouse Cortical Neurons

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Abstract

Activation of glutamate receptors and followed increase of intracellular calcium concentration is a key pathological mechanism involved in secondary neuronal injury after traumatic brain injury (TBI). Stromal interaction molecule (STIM) proteins are considered to be important players in regulating neuronal Ca2+ homeostasis under normal aging and pathological conditions. Here, we investigated the role of STIM1 in regulating metabotropic glutamate receptor 1 (mGluR1)-related Ca2+ signaling and neuronal survival by using an in vitro traumatic neuronal injury (TNI) model. The expression of STIM1 was significantly increased at both mRNA and protein levels after TNI. Down-regulation of STIM1 by specific small interfere RNA significantly preserved neuronal viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell death after traumatic injury. Moreover, knockdown of STIM1 significantly alleviated the mGluR1-related increase of cytoplasmic Ca2+ levels after TNI. By analyzing Ca2+ imaging in Ca2+-free conditions, we demonstrated that the mGluR1-dependent inositol trisphosphate receptor and/or ryanodine receptor-mediated Ca2+ release from the endoplasmic reticulum after TNI is strongly attenuated in the absence of STIM1. Together, our results demonstrate that in the mammalian nervous system, STIM1 is a key regulator of mGluR1-dependent Ca2+ signaling and knockdown of STIM1 might be an effective intervention target in TBI.

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The authors declare that there are no conflicts of interest.

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Correspondence to Shi-Wen Guo.

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Peng-Fei Hou and Zhan-Hui Liu have contributed equally to this work.

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Hou, PF., Liu, ZH., Li, N. et al. Knockdown of STIM1 Improves Neuronal Survival After Traumatic Neuronal Injury Through Regulating mGluR1-Dependent Ca2+ Signaling in Mouse Cortical Neurons. Cell Mol Neurobiol 35, 283–292 (2015). https://doi.org/10.1007/s10571-014-0123-0

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  • DOI: https://doi.org/10.1007/s10571-014-0123-0

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