Tulika Gupta, Mandeep Kaur, Navneet Singla, Bishan Dass Radotra, Daisy Sahni, Parampreet Singh Kharbanda, Sunil K Gupta
{"title":"Reelin Signaling Pathway and Mesial Temporal Lobe Epilepsy: A Causative Link.","authors":"Tulika Gupta, Mandeep Kaur, Navneet Singla, Bishan Dass Radotra, Daisy Sahni, Parampreet Singh Kharbanda, Sunil K Gupta","doi":"10.32598/bcn.2021.2554.1","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis.</p><p><strong>Methods: </strong>The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases.</p><p><strong>Results: </strong>We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases.</p><p><strong>Conclusion: </strong>The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.</p>","PeriodicalId":8701,"journal":{"name":"Basic and Clinical Neuroscience","volume":"14 1","pages":"57-72"},"PeriodicalIF":1.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/7d/BCN-14-57.PMC10279991.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Basic and Clinical Neuroscience","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.32598/bcn.2021.2554.1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis.
Methods: The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases.
Results: We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases.
Conclusion: The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.
期刊介绍：
BCN is an international multidisciplinary journal that publishes editorials, original full-length research articles, short communications, reviews, methodological papers, commentaries, perspectives and “news and reports” in the broad fields of developmental, molecular, cellular, system, computational, behavioral, cognitive, and clinical neuroscience. No area in the neural related sciences is excluded from consideration, although priority is given to studies that provide applied insights into the functioning of the nervous system. BCN aims to advance our understanding of organization and function of the nervous system in health and disease, thereby improving the diagnosis and treatment of neural-related disorders. Manuscripts submitted to BCN should describe novel results generated by experiments that were guided by clearly defined aims or hypotheses. BCN aims to provide serious ties in interdisciplinary communication, accessibility to a broad readership inside Iran and the region and also in all other international academic sites, effective peer review process, and independence from all possible non-scientific interests. BCN also tries to empower national, regional and international collaborative networks in the field of neuroscience in Iran, Middle East, Central Asia and North Africa and to be the voice of the Iranian and regional neuroscience community in the world of neuroscientists. In this way, the journal encourages submission of editorials, review papers, commentaries, methodological notes and perspectives that address this scope.
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