Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes
Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber...
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2024-12-01
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| author | Melis Onay Patrick N. Harter Katherina Weber Albrecht Piiper Marcus Czabanka Karl H. Plate Thomas M. Freiman Florian Gessler Barbara Puhahn-Schmeiser |
| author_facet | Melis Onay Patrick N. Harter Katherina Weber Albrecht Piiper Marcus Czabanka Karl H. Plate Thomas M. Freiman Florian Gessler Barbara Puhahn-Schmeiser |
| author_sort | Melis Onay |
| collection | DOAJ |
| description | Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber sprouting, though the mechanisms remain unclear. Microglia play a role in neurogenesis and synaptic modulation, suggesting they may contribute to epilepsy. This study examines the role of microglia and axonal guidance molecules in neuronal reorganization in TLE. Methods: Nineteen hippocampal samples from patients with TLE undergoing epilepsy surgery were analyzed. Microglial activity (M1/M2-like microglia) and neuronal guidance molecules were assessed using microscopy and semi-automated techniques. Gene expression was evaluated using the nCounter Expression Profiling method. Results: Neuronal cell loss was correlated with decreased activity of the M1 microglial phenotype. In the CA2 region, neuronal preservation was linked to increased mossy fiber sprouting and microglial presence. Neuronal markers such as Deleted in Colorectal Cancer (DCC) and Synaptopodin were reduced in areas of cell death, while Netrin-1 was elevated in the granule cell layer, potentially influencing mossy fiber sprouting. The nCounter analysis revealed downregulation of genes involved in neuronal activity (e.g., NPAS4, BCL-2, GRIA1) and upregulation of IκB, indicating reduced neuroinflammation. Conclusions: This study suggests reduced neuroinflammation in areas of neuronal loss, while regions with preserved neurons showed mossy fiber sprouting associated with microglia, Netrin-1, and DCC. |
| format | Article |
| id | doaj-art-3e8603961bc746a29f1da5abdbd9bf22 |
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| language | English |
| publishDate | 2024-12-01 |
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| series | Biomedicines |
| spelling | doaj-art-3e8603961bc746a29f1da5abdbd9bf222025-08-20T02:00:51ZengMDPI AGBiomedicines2227-90592024-12-011212286910.3390/biomedicines12122869Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression ChangesMelis Onay0Patrick N. Harter1Katherina Weber2Albrecht Piiper3Marcus Czabanka4Karl H. Plate5Thomas M. Freiman6Florian Gessler7Barbara Puhahn-Schmeiser8Department of Internal Medicine I, Goethe University, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, GermanyDepartment of Neuropathology, Ludwig-Maximillians-University Munich, Feodor-Lynen-Str. 23, 81377 Munich, GermanyDepartment of Neuropathology (Edinger Institute), Goethe University, Heinrich-Hoffmann-Straße 7, 60528 Frankfurt am Main, GermanyDepartment of Internal Medicine I, Goethe University, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, GermanyDepartment of Neurosurgery, Goethe University, Schleusenweg 16, 60528 Frankfurt am Main, GermanyDepartment of Neuropathology (Edinger Institute), Goethe University, Heinrich-Hoffmann-Straße 7, 60528 Frankfurt am Main, GermanyDepartment of Neurosurgery, Rostock University Medical Center, Schilingallee 35, 18057 Rostock, GermanyDepartment of Neurosurgery, Rostock University Medical Center, Schilingallee 35, 18057 Rostock, GermanyDepartment of Neurosurgery, Freiburg University Medical Center, Breisacher Str. 64, 79106 Freiburg, GermanyBackground: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber sprouting, though the mechanisms remain unclear. Microglia play a role in neurogenesis and synaptic modulation, suggesting they may contribute to epilepsy. This study examines the role of microglia and axonal guidance molecules in neuronal reorganization in TLE. Methods: Nineteen hippocampal samples from patients with TLE undergoing epilepsy surgery were analyzed. Microglial activity (M1/M2-like microglia) and neuronal guidance molecules were assessed using microscopy and semi-automated techniques. Gene expression was evaluated using the nCounter Expression Profiling method. Results: Neuronal cell loss was correlated with decreased activity of the M1 microglial phenotype. In the CA2 region, neuronal preservation was linked to increased mossy fiber sprouting and microglial presence. Neuronal markers such as Deleted in Colorectal Cancer (DCC) and Synaptopodin were reduced in areas of cell death, while Netrin-1 was elevated in the granule cell layer, potentially influencing mossy fiber sprouting. The nCounter analysis revealed downregulation of genes involved in neuronal activity (e.g., NPAS4, BCL-2, GRIA1) and upregulation of IκB, indicating reduced neuroinflammation. Conclusions: This study suggests reduced neuroinflammation in areas of neuronal loss, while regions with preserved neurons showed mossy fiber sprouting associated with microglia, Netrin-1, and DCC.https://www.mdpi.com/2227-9059/12/12/2869temporal lobe epilepsyhippocampal sclerosismicrogliaM1 phenotypeM2 phenotypeNetrin-1 |
| spellingShingle | Melis Onay Patrick N. Harter Katherina Weber Albrecht Piiper Marcus Czabanka Karl H. Plate Thomas M. Freiman Florian Gessler Barbara Puhahn-Schmeiser Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes Biomedicines temporal lobe epilepsy hippocampal sclerosis microglia M1 phenotype M2 phenotype Netrin-1 |
| title | Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes |
| title_full | Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes |
| title_fullStr | Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes |
| title_full_unstemmed | Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes |
| title_short | Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes |
| title_sort | mossy fiber sprouting in temporal lobe epilepsy the impact of netrin 1 dcc and gene expression changes |
| topic | temporal lobe epilepsy hippocampal sclerosis microglia M1 phenotype M2 phenotype Netrin-1 |
| url | https://www.mdpi.com/2227-9059/12/12/2869 |
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