PirB Overexpression Exacerbates Neuronal Apoptosis by Inhibiting TrkB and mTOR Phosphorylation After Oxygen and Glucose Deprivation Injury

Abstract

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.

TAT-Ngn2 Enhances Cognitive Function Recovery and Regulates Caspase-Dependent and Mitochondrial Apoptotic Pathways After Experimental Stroke

“…Moreover, levels of the pro-apoptotic cleaved caspase-3 decreased after TAT-Ngn2 or ngn2 overexpression treatment after reperfusion injury. These observations were consistent with previous studies (Deng et al, 2014; Liu et al, 2017; Zhao et al, 2017). In addition, Bcl-2 downregulation and Bax up-regulation also contribute to CytC release from the mitochondria and result in the activation effect of caspase-9 on caspase-3, finally promoting apoptosis (Guégan et al, 2006; Song et al, 2010; Ji et al, 2012).…”

“…Another study also showed that huperzine A can attenuate apoptosis in hippocampal HT22 cells by activating BDNF/TrkB to enhance Bcl-2 expression and inhibit Bax expression (Mao et al, 2016). Furthermore, inhibiting the phosphorylation of TrkB decreased Bcl-2 expression and increased Bax expression, which induced mitochondria to release CytC and activate caspase-3, ultimately leading to increased cell apoptosis activity in the OGD model, as demonstrated in our previous study (Zhao et al, 2017). In the present study, the pro-apoptotic cleaved caspase-3 and Bax decreased and the anti-apoptotic protein Bcl-2 increased after treatment with TAT-Ngn2 or ngn2 overexpression after reperfusion injury, which was consistent with previous studies.…”

“…Lee et al (2017) reported that Ngn2 protein-transduced human NPCs significantly upregulated the gene expression levels of BDNF, increased cell survival and enhanced structural and functional recovery in a mouse model of neonatal HI brain injury. In our previous study, we found that inhibition of TrkB phosphorylation increased neuronal damage and apoptosis after OGD injury (Zhao et al, 2017). These studies indicated that Ngn2 is involved in the regulation of BDNF and p-TrkB expression, which may play an important role in neuronal survival after cerebral ischemic injury.…”

“…Global cerebral ischemic injury is commonly observed in clinical conditions such as cardiac arrest and stroke (Tiainen et al, 2015), which mainly attack vulnerable brain regions, such as the CA1 region in the hippocampus (Li et al, 2017), leading to neuronal apoptosis and neurological deficit in memory (Sabri et al, 2013; Zhao et al, 2017). However, there is currently no effective therapy.…”

Establishment of axon regeneration regulatory network and the role of low intensity pulsed ultrasound in the network

“…Bochner et al (2014) pointed out in 2014 that closed PirB function is conducive to visual cortical neuronal function recovery. The latest report by Zhao et al (2016b) in 2016 showed that PirB over-expression could cause apoptosis of in vitro cultured cortical neurons after ischemia and reperfusion. PilB is co-receptor of the central nervous system myelin-associated inhibitory proteins (MAIs): Nogo-A, Myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), which have high affinity and exhibit a chronic inhibitory effect on axonal growth (Omoto et al, 2010).…”