MTOR/autophagy pathway in the hippocampus of rats suffering intermittent hypoxia preconditioning and global cerebral ischemia-reperfusion.

Ya-Ning Zhao,Cheng-Jing Xu,Chang-Xiang Chen,Xiang-Fei Guo,Shu-Xing Li,Jian-Min Li

doi:10.18632/oncotarget.15058

Ya-Ning Zhao, Cheng-Jing Xu + Show 4 more

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https://doi.org/10.18632/oncotarget.15058

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Abstract

We explored the role of mTOR/autophagy pathway in the aggravation of cerebral ischemia-reperfusion nerve injury caused by intermittent hypoxia. Eighty male wistar rats were divided into four groups by the random number method: sham operation group (SO group, n=20), cerebral ischemia-reperfusion group (I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group (IH+I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group plus mTOR inhibitor group (inhibitor group, n=20). The results showed that compared with the SO group, HE staining showed structural damage of neurons at each time point, the immunohistochemical assay showed an increasing number of mTOR and beclin1 immune-positive cells (P<0.05) and RT-PCR showed enhanced expression of mTOR and beclin1 protein in the I/R group (P<0.05). Compared with the I/R group, HE staining showed exacerbating structural damage of neurons at each time point, the immunohistochemical assay showed an increasing number of mTOR and beclin1 immune-positive cells (P<0.05) and RT-PCR showed enhanced expression of mTOR and beclin1 protein in the IH+I/R group (P<0.05). Compared with the IH+I/R group, HE staining showed remissive structural damage of neurons at each time point, the immunohistochemical assay showed a decreasing number of mTOR immune-positive cells and a rising number of beclin1immune-positive cells (P<0.05) and RT-PCR showed weakened expression of mTOR protein and enhanced expression of beclin1 protein in the inhibitor group (P<0.05). Thence, the present study indicated that intermittent hypoxia preconditioning can aggravate the nerve injury of the global cerebral ischemia-reperfusion model, and the mechanism is associated with the activation of mTOR/autophagy pathway.

Highlights

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor of cerebral arterial thrombosis, which can aggravate the cerebral injury caused by cerebral arterial thrombosis [1,2]
We used rats with intermittent hypoxia preconditioning to prepare global cerebral ischemia-reperfusion models, observed the expression of Mammalian target of rapamycin (mTOR)/autophagy pathway and the loss and changes of nerve cells in the rat hippocampus and investigated its role in the aggravation of cerebral ischemia-reperfusion neuron injury caused by intermittent hypoxia, so as to provide experimental basis for the prevention and cure of OSAHS complicated with ischemic cerebrovascular diseases
MTOR manifests as a brown color after immunohistochemical staining, and it is located in cytoplasm and primarily expressed in neurons. mTOR immune-positive cells were rarely seen in the SO group; compared with the SO group, the I/R group showed an increased number of mTOR immune-positive cells at each time point (P

Summary

Introduction

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor of cerebral arterial thrombosis, which can aggravate the cerebral injury caused by cerebral arterial thrombosis [1,2]. Autophagy, which widely exists in cerebrovascular diseases such as cerebral arterial thrombosis, exerts significant effects on the pathological process of cerebral arterial thrombosis via regulating apoptosis of nerve cells [3,4]. We speculate that www.impactjournals.com/oncotarget mTOR/autophagy-associated pathways play an important role in the pathological process of the aggravation of cerebral ischemia nerve injury caused by intermittent hypoxia. We used rats with intermittent hypoxia preconditioning to prepare global cerebral ischemia-reperfusion models, observed the expression of mTOR/autophagy pathway and the loss and changes of nerve cells in the rat hippocampus and investigated its role in the aggravation of cerebral ischemia-reperfusion neuron injury caused by intermittent hypoxia, so as to provide experimental basis for the prevention and cure of OSAHS complicated with ischemic cerebrovascular diseases

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