PirB Overexpression Exacerbates Neuronal Apoptosis by Inhibiting TrkB and mTOR Phosphorylation After Oxygen and Glucose Deprivation Injury
Previous studies have proven that paired immunoglobulin-like receptor B (PirB) plays a crucial suppressant role in neurite outgrowth and neuronal plasticity after central nervous system injury. However, the role of PirB in neuronal survival after cerebral ischemic injury and its mechanisms remains unclear. In the present study, the role of PirB is investigated in the survival and apoptosis of cerebral cortical neurons in cultured primary after oxygen and glucose deprivation (OGD)-induced injury. The results have shown that rebarbative PirB exacerbates early neuron apoptosis and survival. PirB gene silencing remarkably decreases early apoptosis and promotes neuronal survival after OGD. The expression of bcl-2 markedly increased and the expression of bax significantly decreased in PirB RNAi-treated neurons, as compared with the control- and control RNAi-treated ones. Further, phosphorylated TrkB and mTOR levels are significantly downregulated in the damaged neurons. However, the PirB silencing markedly upregulates phosphorylated TrkB and mTOR levels in the neurons after the OGD. Taken together, the overexpression of PirB inhibits the neuronal survival through increased neuron apoptosis. Importantly, the inhibition of the phosphorylation of TrkB and mTOR may be one of its mechanisms.
KeywordsPirB OGD Neuronal survival Apoptosis TrkB mTOR
This work was supported by grants from the National Natural Science Foundation of China (No. 81501207, 81500063, 81471265, 81271290 and 81471415) and the Fourth Military Medical University Foundation (No. 2013-D03).
Compliance with Ethical Standards
Conflict of Interest
The authors declare no conflict of interest.
- Annovazzi L, Mellai M, Caldera V, Valente G, Tessitore L, Schiffer D (2009) MTOR, S6 and AKT expression in relation to proliferation and apoptosis/autophagy in glioma. Anticancer Res 8:3087–3094Google Scholar
- Israelsson C, Flygt J, Astrand E, Kiwanuka O, Bengtsson H, Marklund N (2014) Altered expression of myelin-associated inhibitors and their receptors after traumatic brain injury in the mouse. Restor Neurol Neurosci 5:717–731Google Scholar
- Mu D (2012) PirB restricts neuronal regeneration in developing rat brain following hypoxia-ischemia. Mol Med Rep 2:339–344Google Scholar
- Peng WS, Qi C, Zhang H, Gao ML, Wang H, Ren F et al (2015) Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury. Neural Regen Res 7:1139–1146Google Scholar
- Wang H, Mu DZ (2014) [Neuroregeneration of newborn rats with hypoxic-ischemic brain damage following antibody-mediated neutralization of paired-immunoglobulin-like receptor B. Zhongguo Dang Dai Er Ke Za Zhi 1:67–72Google Scholar