Contributions
Abstract: EP1436
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Objective: The objective is to explore if and how mitochondria contribute to disease mechanisms in multiple sclerosis.
Methods:Articles were found through keyword-based search in the database ”PubMed”. All types of studies, except case studies, were included. Articles on all subtypes of MS and mitochondrial dysfunction in other brain disorders were included. Data from autopsy, animal and human studies were included. Hereditary mitochondrial diseases and mitochondrial dysfunction in conditions outside the brain were excluded. Triangulation of the material was used to minimize risk of bias.
Results: Oxidative stress mediated by activated microglia and macrophages is found in all lesions at all stages of MS. These cells are found to up-regulate enzymes involved in radical production. Oxidative and nitrosative stress inhibit mitochondrial activity and induce DNA deletions. Mitochondrial dysfunction widespread in the brain of MS patients. Demyelination causes a higher energy demand in neurons, causing compensatory changes in mitochondria. Axonal loss is especially profound in active inflammatory lesions, and occurs shortly after demyelination. In addition, a global non-inflammatory neurodegeneration is detected in lesions and normal-appearing brain matter.
Conclusion: During early stages the inflammatory response and oxidative stress causes demyelination, neuronal loss and may induce mitochondrial dysfunction. Mitochondrial dysfunction could lead to increased oxidative stress, energy failure in neurons and trigger pro-apoptotic events. Disease mechanisms at early stages are considered inflammatory, where surrounding glia cells may respond in a predetermined manner with profound influence on neurons and infiltrating leukocytes. At late stages, the inflammatory response is significantly lower. Progressive neuronal loss may be a result of secondary Wallerian degeneration, oxidative stress and/or mitochondrial dysfunction. Mitochondrial dysfunction in MS is potentially an important secondary cause of tissue injury.
Disclosure:
Helene Hovden: Nothing to disclose.
Jette Lautrup Frederiksen: Nothing to disclose
Abstract: EP1436
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
Objective: The objective is to explore if and how mitochondria contribute to disease mechanisms in multiple sclerosis.
Methods:Articles were found through keyword-based search in the database ”PubMed”. All types of studies, except case studies, were included. Articles on all subtypes of MS and mitochondrial dysfunction in other brain disorders were included. Data from autopsy, animal and human studies were included. Hereditary mitochondrial diseases and mitochondrial dysfunction in conditions outside the brain were excluded. Triangulation of the material was used to minimize risk of bias.
Results: Oxidative stress mediated by activated microglia and macrophages is found in all lesions at all stages of MS. These cells are found to up-regulate enzymes involved in radical production. Oxidative and nitrosative stress inhibit mitochondrial activity and induce DNA deletions. Mitochondrial dysfunction widespread in the brain of MS patients. Demyelination causes a higher energy demand in neurons, causing compensatory changes in mitochondria. Axonal loss is especially profound in active inflammatory lesions, and occurs shortly after demyelination. In addition, a global non-inflammatory neurodegeneration is detected in lesions and normal-appearing brain matter.
Conclusion: During early stages the inflammatory response and oxidative stress causes demyelination, neuronal loss and may induce mitochondrial dysfunction. Mitochondrial dysfunction could lead to increased oxidative stress, energy failure in neurons and trigger pro-apoptotic events. Disease mechanisms at early stages are considered inflammatory, where surrounding glia cells may respond in a predetermined manner with profound influence on neurons and infiltrating leukocytes. At late stages, the inflammatory response is significantly lower. Progressive neuronal loss may be a result of secondary Wallerian degeneration, oxidative stress and/or mitochondrial dysfunction. Mitochondrial dysfunction in MS is potentially an important secondary cause of tissue injury.
Disclosure:
Helene Hovden: Nothing to disclose.
Jette Lautrup Frederiksen: Nothing to disclose