Effect of the JAK2/STAT3 signaling pathway on nerve cell apoptosis in rats with white matter injury

X.-M. Chen, Y.-H. Yu, L. Wang, X.-Y. Zhao, J.-R. Li

Department of Neurology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China. ljry612@163.com

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• Neurology

OBJECTIVE: The Janus activated kinase 2 (JAK2)/signal transducer and the activator of transcription 3 (STAT3) pathway are involved in many physiological processes, such as cell survival, inflammation, development, proliferation and differentiation. Increasing evidence has shown that this pathway also has neuron-specific functions in the central nervous system. In this study, the functional significance of the JAK2/STAT3 signaling pathway in nerve cell apoptosis in rats with white matter injury was evaluated.

MATERIALS AND METHODS: The rat model of white matter injury was established by ligating bilateral common carotid arteries, and the changes of the JAK2 and STAT3 phosphorylation in hippocampal neurons were evaluated using the immunohistochemistry. In addition, the effects of JAK2 inhibitor AG490 and STAT3 small interfering ribonucleic acids (siRNAs) on the expression of phosphorylated-JAK2 (pJAK2), STAT3 messenger RNAs (mRNAs) and pSTAT3 in hippocampal neurons of white matter injury rats were studied. The effects of both on cerebral infarction volume and neuron apoptosis in white matter injury rats were also investigated.

RESULTS: The expression of pJAK2 and pSTAT3 were significantly increased after white matter injury in rats (p<0.05). JAK2 inhibitor AG490 markedly decreased the phosphorylation of JAK2 and STAT3 in hippocampal neurons in the model group (p<0.05). STAT3 siRNAs remarkably reduced the expression levels of STAT3 mRNA and protein in hippocampus neurons in the model group (p<0.05), while having no effect on the expression level of pJAK2 protein. AG490 and STAT3 siRNAs notably attenuated the volume of cerebral infarction in the model group, as well as reduced neuron apoptosis after white matter injury.

CONCLUSIONS: The inhibition of the JAK2/STAT3 signaling pathway contributed to reducing the volume of cerebral infarction and neuron apoptosis in rats with white matter injury.

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