The expression of glutamate receptor 5 in brain tissue of human intractable temporal lobe epilepsy_West China Medical Journal

Authors：

ZENG Yijun ^1,2 , YU Shui ² , LEI Ding ¹ ,  ZHANG Heng ¹ , LI Jinmei ³ , ZHOU Zhangming ²

1. Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Neurosurgery, Dujiangyan Medical Center, Dujiangyan, Sichuan 611830, P. R. China;
3. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

ZHANG Heng, Email: zhanghengcn@gmail.com

Keywords：

Kainate receptor; Glutamate receptor 5; Intractable temporal lobe epilepsy; Rhesus

DOI：

10.7507/1002-0179.201604129

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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.

Citation： ZENG Yijun, YU Shui, LEI Ding, ZHANG Heng, LI Jinmei, ZHOU Zhangming. The expression of glutamate receptor 5 in brain tissue of human intractable temporal lobe epilepsy. West China Medical Journal, 2017, 32(5): 659-664. doi: 10.7507/1002-0179.201604129 Copy

1.	Zentner J, Hufnagel A, Wolf HK, et al. Surgical treatment of neoplasms associated with medically intractable epilepsy. Neurosurgery, 1997, 41(2): 378-386; discussion 386-387.
2.	Baran H, Gramer M, Hönack D, et al. Systemic administration of kainate induces marked increases of endogenous kynurenic acid in various brain regions and plasma of rats. Eur J Pharmacol, 1995, 286(2): 167-175.
3.	Ben-Ari Y, Cossart R. Kainate, a double agent that generates seizures: two decades of progress. Trends Neurosci, 2000, 23(11): 580-587.
4.	Ben-Ari Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience, 1985, 14(2): 375-403.
5.	Hollmann M, Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci, 1994, 17: 31-108.
6.	Vincent P, Mulle C. Kainate receptors in epilepsy and excitotoxicity. Neuroscience, 2009, 158(1): 309-323.
7.	Westbrook GL, Lothman EW. Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity. Brain Res, 1983, 273(1): 97-109.
8.	庾蕾, 刘建平, 庄志雄, 等. 实时 RT-PCR 基因表达相对定量 REST(C) 软件分析与 2^(-△△CT) 法比较. 热带医学杂志, 2007, 7(10): 956-958.
9.	Sommer B, Seeburg PH. Glutamate receptor channels: novel properties and new clones. Trends Pharmacol Sci, 1992, 13(7): 291-296.
10.	Huntley GW, Rogers SW, Moran T, et al. Selective distribution of kainate receptor subunit immunoreactivity in monkey neocortex revealed by a monoclonal antibody that recognizes glutamate receptor subunits GluR5/6/7. J Neurosci, 1993, 13(7): 2965-2981.
11.	Li H, Rogawski MA. GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdalain vitro. Neuropharmacology, 1999, 37(10/11): 1279-1286.
12.	Kaminski RM, Banerjee M, Rogawski MA. Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology, 2004, 46(8): 1097-1104.
13.	Smolders I, Bortolotto ZA, Clarke VR, et al. Antagonists of GLU(K5)-containing kainate receptors prevent pilocarpine-induced limbic seizures. Nat Neurosci, 2002, 5(8): 796-804.
14.	Mathern GW, Pretorius JK, Kornblum HI, et al. Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients. Neurobiol Dis, 1998, 5(3): 151-176.
15.	DeFelipe J, Huntley GW, Del Río MR, et al. Microzonal decreases in the immunostaining for non-NMDA ionotropic excitatory amino acid receptor subunits GluR 2/3 and GluR 5/6/7 in the human epileptogenic neocortex. Brain Res, 1994, 657(1/2): 150-158.
16.	Ullal G, Fahnestock M, Racine R. Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5, GluR6, and GluR7 mRNA and protein expression in rat hippocampus. Epilepsia, 2005, 46(5): 616-623.
17.	Kudo Y, Niwa H, Tanaka A, et al. Actions of picrotoxinin and related compounds on the frog spinal cord: the role of a hydroxyl-group at the 6-position in antagonizing the actions of amino acids and presynaptic inhibition. Br J Pharmacol, 1984, 81(2): 373-380.

1. Zentner J, Hufnagel A, Wolf HK, et al. Surgical treatment of neoplasms associated with medically intractable epilepsy. Neurosurgery, 1997, 41(2): 378-386; discussion 386-387.
2. Baran H, Gramer M, Hönack D, et al. Systemic administration of kainate induces marked increases of endogenous kynurenic acid in various brain regions and plasma of rats. Eur J Pharmacol, 1995, 286(2): 167-175.
3. Ben-Ari Y, Cossart R. Kainate, a double agent that generates seizures: two decades of progress. Trends Neurosci, 2000, 23(11): 580-587.
4. Ben-Ari Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience, 1985, 14(2): 375-403.
5. Hollmann M, Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci, 1994, 17: 31-108.
6. Vincent P, Mulle C. Kainate receptors in epilepsy and excitotoxicity. Neuroscience, 2009, 158(1): 309-323.
7. Westbrook GL, Lothman EW. Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity. Brain Res, 1983, 273(1): 97-109.
8. 庾蕾, 刘建平, 庄志雄, 等. 实时 RT-PCR 基因表达相对定量 REST(C) 软件分析与 2^(-△△CT) 法比较. 热带医学杂志, 2007, 7(10): 956-958.
9. Sommer B, Seeburg PH. Glutamate receptor channels: novel properties and new clones. Trends Pharmacol Sci, 1992, 13(7): 291-296.
10. Huntley GW, Rogers SW, Moran T, et al. Selective distribution of kainate receptor subunit immunoreactivity in monkey neocortex revealed by a monoclonal antibody that recognizes glutamate receptor subunits GluR5/6/7. J Neurosci, 1993, 13(7): 2965-2981.
11. Li H, Rogawski MA. GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdalain vitro. Neuropharmacology, 1999, 37(10/11): 1279-1286.
12. Kaminski RM, Banerjee M, Rogawski MA. Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology, 2004, 46(8): 1097-1104.
13. Smolders I, Bortolotto ZA, Clarke VR, et al. Antagonists of GLU(K5)-containing kainate receptors prevent pilocarpine-induced limbic seizures. Nat Neurosci, 2002, 5(8): 796-804.
14. Mathern GW, Pretorius JK, Kornblum HI, et al. Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients. Neurobiol Dis, 1998, 5(3): 151-176.
15. DeFelipe J, Huntley GW, Del Río MR, et al. Microzonal decreases in the immunostaining for non-NMDA ionotropic excitatory amino acid receptor subunits GluR 2/3 and GluR 5/6/7 in the human epileptogenic neocortex. Brain Res, 1994, 657(1/2): 150-158.
16. Ullal G, Fahnestock M, Racine R. Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5, GluR6, and GluR7 mRNA and protein expression in rat hippocampus. Epilepsia, 2005, 46(5): 616-623.
17. Kudo Y, Niwa H, Tanaka A, et al. Actions of picrotoxinin and related compounds on the frog spinal cord: the role of a hydroxyl-group at the 6-position in antagonizing the actions of amino acids and presynaptic inhibition. Br J Pharmacol, 1984, 81(2): 373-380.

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