Volume 14, Issue 1 (January & February 2023)
BCN 2023, 14(1): 57-72 |
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Gupta T, Kaur M, Singla N, Radotra B D, Sahni D, Kharbanda P S et al . Reelin Signaling Pathway and Mesial Temporal Lobe Epilepsy: A Causative Link. BCN 2023; 14 (1) :57-72
URL: http://bcn.iums.ac.ir/article-1-1788-en.html
URL: http://bcn.iums.ac.ir/article-1-1788-en.html
Tulika Gupta * 
1, Mandeep Kaur1 
, Navneet Singla2 , Bishan Dass Radotra3 , Daisy Sahni1 , Parampreet Singh Kharbanda4 , Sunil K Gupta2
1, Mandeep Kaur1 , Navneet Singla2 , Bishan Dass Radotra3 , Daisy Sahni1 , Parampreet Singh Kharbanda4 , Sunil K Gupta2
1- Department of Anatomy, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
2- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
3- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
4- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
2- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
3- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
4- Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
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.
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.
Keywords: Reelin, Apolipoprotein E receptor 2 (ApoER2), Very low-density lipoprotein receptor (VLDLR), Disabled 1 (Dab1), Matrix metalloproteinase 9 (MMP-9), Tissue inhibitor of metalloproteases-1 (TIMP-1)
Type of Study: Original |
Subject:
Cellular and molecular Neuroscience
Received: 2020/05/13 | Accepted: 2020/10/10 | Published: 2023/01/1
Received: 2020/05/13 | Accepted: 2020/10/10 | Published: 2023/01/1
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