Objective To discuss the correlation between glutamate receptor 5 (GLUR5) and the pathogenesis of intractable temporal lobe epilepsy (ITLE), through detecting the GLUR5 expression in human with ITLE and Coriaria lactone-induced rhesus monkey temporal lobe epilepsy model. Methods Fifty-four patients with ITLE treated in West China Hospital between January 2007 and December 2015 were regarded as clinical case group in this study. The other 43 patients who underwent temporal lobe removal decompression surgery in the same time period due to trauma, tumor or large area cerebral hemorrhage complicated with cerebral hernia were designated as the clinical control group. Quantitive polymerase chain reaction (PCR) and Western blot methods were used to detect mRNA and protein levels of GLUR5. Western blot was also used to detect the GLUR5 protein level in the hippocampus and temporal lobe tissues of Coriaria lactone-induced rhesus monkey epilepsy model, and the result was compared with that of animal controls. Results Quantitive PCR results showed that the expression ratio (R value) of GLUR5 in the temporal lobe of the clinical case group to the clinical control group was 0.262, without significant difference (P>0.05), while theR value in the hippocampus was 4.896, with a significant difference (P<0.05). The amplification curve showed that the GLUR5 level in the hippocampus of the clinical case group was higher than that of the clinical control group, but the GLUR5 mRNA level in the temporal lobe tissue was not significantly changed. GLUR5 PCR amplified product electrophoresis showed that the amplified fragment was 161 bp. Western blot analysis showed that the GLUR5/actin value of the temporal lobe tissue in the clinical case group was 2.172±0.063, while the value in the clinical control group was 2.142±0.060, and the difference was not statistically significant (P>0.05). The GLUR5/actin value of the hippocampus in the clinial case group was 2.548±0.509, while it was 1.584±0.415 in the clinial control group, and the difference was statistically significant (P<0.05). The GLUR5/actin value of the hippocampus of the rhesus monkey model of epilepsy was 1.007±0.034, and it was 1.001±0.032 in the animal control group, and the difference was not statistically significant (P>0.05). The GLUR5/actin value of the temporal lobe tissue in the animal experimental group of rhesus model of epilepsy was 0.763±0.026, and it was 0.742±0.034 in the animal control group, and the difference was not statistically significant (P>0.05). The target protein bands showed that GLUR5 protein expression in the temporal lobe tissue and hippocampus of the rhesus model of epilepsy and animal controls was not significantly different (P>0.05). Conclusions GLUR5 participates in the pathogenesis of human ITLE by acting on the hippocampus. The expression of GLUR5 in human ITLE is abnormal, but the expression of GLUR5 is not changed in the rhesus model of epilepsy. The abnormal expression of GLUR5 may play a role in the pathogenesis of ITLE.
ObjectiveThe abnormal autophagy fluxis involved in the pathophysiological process of drug-resistance temporal lobe epilepsy (TLE).Hippocampal sclerosis (HS) is the main pathological type of drug-resistance TLE.Different subtypes of HS have various prognosis, etiology and pathophysiology.However, whether theabnormal block ofautophagy flux involved in this process has not been reported.This study proposed a preliminary comparison of autophagy fluxin typical and atypical HS to investigate the potential pathogenesis and drug-resistance mechanism of atypical HS. MethodsSurgical excision of hippocampal and temporal lobe epilepsy foci were performed in 17 patients with drug-resistance TLE.Patients were grouped according to the HS classification issued by International League Against Epilepsy in 2013.The distribution and expression of LC3B, beclin-1 and P62 were detected by immunohistochemistry and Western blot in each group. ResultsLC3B, beclin-1 and P62 are mainly expressed in neuronal cytoplasm, which is consistent with previous reports.Taking β-actin as internal reference, we found that LC3B and Beclin-1, the downstream products of autophagy flux, have increased significantly (P < 0.01) in the atypical HS group compared to typical HS group.However, the autophagy flux substrate P62 has no difference between the groups.This result suggested that compared with the typical HS group, atypical HS group had autophagy substrate accumulation and autophagy flux abnormal block.Besides, we found that glyceraldehycle-3-phosphate dehydrogenase(GAPDH) was significantly different between the two groups (P=0.003). ConclusionThere is abnormal phenomenon of autophagy flux in atypical HS, and GAPDH elevation may be involved in its mechanism, which might provide new targets and ideas for future treatment of atypical HS.