Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE)
Abstract Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug‐resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabol...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.12871 |
| _version_ | 1827357798584811520 |
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| author | Claudia Manca Roberta Coa Elisabetta Murru Gianfranca Carta Giovanni Pinna Roberto Sanfilippo Lorenzo Polizzi Marco Pistis Paolo Follesa Monica Puligheddu Sebastiano Banni |
| author_facet | Claudia Manca Roberta Coa Elisabetta Murru Gianfranca Carta Giovanni Pinna Roberto Sanfilippo Lorenzo Polizzi Marco Pistis Paolo Follesa Monica Puligheddu Sebastiano Banni |
| author_sort | Claudia Manca |
| collection | DOAJ |
| description | Abstract Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug‐resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator‐activated receptor α (PPARα) and sirtuin1 (SIRT1) genes—key regulators in energy and lipid metabolism—and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPARα expression and erythrocyte concentrations of PPARα ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPARα may provide innovative therapeutic strategies for managing DRE. Plain Language Summary: The exact mechanism of VNS is still unknown. This study investigated the effects of VNS Therapy on energetic metabolism, suggesting possible novel biomarkers for DRE subjects and neuromodulation therapies. |
| first_indexed | 2024-03-08T05:53:13Z |
| format | Article |
| id | doaj.art-01ed09ea9d3044a88dab517ebe533868 |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-03-08T05:53:13Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-01ed09ea9d3044a88dab517ebe5338682024-02-05T06:37:58ZengWileyEpilepsia Open2470-92392024-02-019143243810.1002/epi4.12871Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE)Claudia Manca0Roberta Coa1Elisabetta Murru2Gianfranca Carta3Giovanni Pinna4Roberto Sanfilippo5Lorenzo Polizzi6Marco Pistis7Paolo Follesa8Monica Puligheddu9Sebastiano Banni10Department of Biomedical Sciences Division of Physiology University of Cagliari Cagliari ItalyCenter for the Diagnosis and Treatment of Adult Epilepsy Neurology Unit AOU Cagliari Cagliari ItalyDepartment of Biomedical Sciences Division of Physiology University of Cagliari Cagliari ItalyDepartment of Biomedical Sciences Division of Physiology University of Cagliari Cagliari ItalySC Neurosurgery Neuroscience and Rehabilitation Department, San Michele Hospital ARNAS G. Brotzu Cagliari ItalySC Vascular Surgery AOU Cagliari Cagliari ItalyCenter for the Diagnosis and Treatment of Adult Epilepsy Neurology Unit AOU Cagliari Cagliari ItalyDepartment of Biomedical Sciences Division of Neuroscience and Clinical Pharmacology University of Cagliari Cagliari ItalyDepartment of Life and Environmental Sciences Section of Neuroscience and Anthropology University of Cagliari Cagliari ItalyCenter for the Diagnosis and Treatment of Adult Epilepsy Neurology Unit AOU Cagliari Cagliari ItalyDepartment of Biomedical Sciences Division of Physiology University of Cagliari Cagliari ItalyAbstract Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug‐resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator‐activated receptor α (PPARα) and sirtuin1 (SIRT1) genes—key regulators in energy and lipid metabolism—and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPARα expression and erythrocyte concentrations of PPARα ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPARα may provide innovative therapeutic strategies for managing DRE. Plain Language Summary: The exact mechanism of VNS is still unknown. This study investigated the effects of VNS Therapy on energetic metabolism, suggesting possible novel biomarkers for DRE subjects and neuromodulation therapies.https://doi.org/10.1002/epi4.12871bioactive moleculesenergy and lipid metabolismfatty acidsneuromodulationPPARαSIRT1 |
| spellingShingle | Claudia Manca Roberta Coa Elisabetta Murru Gianfranca Carta Giovanni Pinna Roberto Sanfilippo Lorenzo Polizzi Marco Pistis Paolo Follesa Monica Puligheddu Sebastiano Banni Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE) Epilepsia Open bioactive molecules energy and lipid metabolism fatty acids neuromodulation PPARα SIRT1 |
| title | Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE) |
| title_full | Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE) |
| title_fullStr | Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE) |
| title_full_unstemmed | Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE) |
| title_short | Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug‐resistant epilepsy (DRE) |
| title_sort | identification of metabolic biomarkers of chronic vagus nerve stimulation vns in subjects with drug resistant epilepsy dre |
| topic | bioactive molecules energy and lipid metabolism fatty acids neuromodulation PPARα SIRT1 |
| url | https://doi.org/10.1002/epi4.12871 |
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