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| The Expression of Zinc α2 Glycoprotein in Temporal Lobe Epilepsy and Its Correlation with CaMK Ⅱ Phosphorylation and HCN |
| DUAN Xiaomei, XIAO Zijian, YE Qing, et al |
| The First Affiliated Hospital of University of South China, Hunan Hengyang 421001, China |
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Abstract Objective: To explore the expression of Zinc alpha-2 glycoprotein (ZAG) in temporal lobe epilepsy (TLE) and its correlation with CaMKⅡ and HCN channels. Methods: Adeno associated virus vectors (AAV-ZAG and AAV-NC) were injected into the unilateral ventricle of rats. Three weeks later, Pilocarpine hydrochloride (PHCL) was intraperitoneally injected to construct a TLE model. Three days before modeling, CaMKII inhibitor KN-93 was intraperitoneally injected and randomly divided into eight groups: control group, model group, AAV-NC+model group, AAV-ZAG+model group, AAV-NC+saline group, AAV-NC+KN-93 group, AAV-ZAG+saline group, and AAV-ZAG+KN-93 group. Record the time of the first occurrence of grade IV or above epilepsy after injection of PHCL and the number of spontaneous epileptic seizures in the 5th week; Immunofluorescence detection of ZAG and GFAP expression in rat hippocampal tissue; WB detection of the expression levels of ZAG, p-CaMKII, HCN1, and HCN2 in rat hippocampal tissue. Results: The expression of ZAG in the hippocampal tissue of TLE rats was significantly downregulated (P<0.05); overexpression of ZAG in hippocampal tissue can significantly prolong the latency of TLE (P<0.05), reduce the number of seizures (P<0.05), decrease the number of GFAP positive cells (P<0.05), upregulate the expression levels of HCN1, HCN2, and p-CaMKII (P<0.05), but the addition of CaMKII inhibitors can reverse these effects. Conclusion: ZAG regulates HCN channel protein activity by promoting CaMKII phosphorylation, thereby improving TLE.
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2025, Vol. 31 
