Silencing C-X-C motif chemokine receptor inhibited autophagy of hippocampal neurons in epileptic mice by upregulating TWIK-related K(+) Channel 1.

OBJECTIVE: Epilepsy is a neurological disease whose onset causes a variety of sequelae, reducing the standard of living. TWIK-related K(+) channel 1 (TREK-1) has been linked to epilepsy. C-X-C motif chemokine receptor (CXCR2) is a potential target for the treatment of epilepsy inflammation. This work aims to observe the effect of CXCR2 expression on neuron autophagy and TREK-1 expression in the hippocampus of epileptic mice. MATERIAL AND METHODS: An animal model of epilepsy was established, and the CXCR2 gene was silenced. The expression of TREK-1, interleukin (IL)-1b, tumor necrosis factor-a, and IL-6 in the hippocampus of mice was detected by quantitative real-time polymerase chain reaction. Autophagy-related proteins beclin-1 and microtubule-associated protein light chain 3 (LC3) were examined by Western blot. Cell proliferation and activity were analyzed using cell counting kit-8 and 5-Bromodeoxyuridine assays. RESULTS: Compared with that in the normal group, TREK-1 expression decreased and CXCR2 expression increased significantly in the hippocampus of epileptic model mice (P < 0.01). Two autophagy markers, beclin-1 and LC3 II/LC3 I, showed an increased expression in the hippocampal regions of the epileptic model group (P < 0.01). In addition, B-cell lymphoma 2 (Bcl-2)-associated X protein levels increased and Bcl-2 levels decreased in the epileptic mice (P < 0.01). After CXCR2 silencing, the expression of proinflammatory factor in the hippocampus of epileptic mice significantly decreased (P < 0.01). In vitro, cell viability and proliferation increased significantly after silencing CXCR2 (P < 0.05). Meanwhile, the expression levels of TREK-1 and Bcl-2 significantly increased (P < 0.001) and the levels of autophagy markers decreased in vivo and in vitro (P < 0.01). In vivo, CXCR2 expression did not change significantly after silencing TREK-1. After silencing TREK-1 and overexpressing CXCR2, the proliferation ability of HT22 cells decreased significantly (P < 0.001). CONCLUSION: Epileptic mice's hippocampal neuronal damage can be ameliorated by CXCR2 suppression. One possible explanation is that epileptic mice's hippocampus tissues express more TREK-1, which prevents excessive neuronal autophagy and lowers apoptosis.