Identificador: TDX:2639
Autors: Martínez López, Nohora Milena
Resum:
Neurodegeneration in the central nervous system is associated with loss of neuronal structure and function, reduced survival and increased neuronal death, generating functional and mental alterations in the individual. There is a link between chronic inflammation and neurodegeneration. Activation of inflammatory processes has been observed in neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, among others. Inflammation does not typically represent the triggering factor in neurodegenerative diseases, but the sustained inflammatory response, related to glial activation, contributes to the progression of the disease. Persistent inflammation may induce and/or exacerbate neurodegeneration.
Melatonin, leptin and omega-3 fatty acids have anti-inflammatory properties. However, the mechanisms by which these effects occur are poorly understood at the level of the central nervous system.
The objective of this thesis was to study the potential anti-inflammatory and/or neuroprotective effects of melatonin, leptin and fatty acids: docosahexaenoic, eicosapentaenoic and palmitic in cultures of glial cells from mouse C57BL/6J. We worked with primary cultures of glia from the mouse cortex, which were exposed to glial activation with pro-inflammatory cytokines IFNγ, IL-1β and TNFα. They were pre-treated with melatonin, leptin and fatty acids and subsequently treated with pro-inflammatory cytokines.
The results showed that exposure of glial cells to proinflammatory cytokines increases nitric oxide production, expression of inducible nitric oxide synthase (iNOS), and activation of the JNK, p38, c-JUN, ERK ½ and JAK / STAT. It was observed that melatonin, leptin and omega-3 fatty acids (at low concentrations) do not affect cell viability and decrease nitric oxide production, inhibit the production of iNOS and the activation of p38 MAPK. Melatonin, leptin, DHA and EPA could be considered as a promising therapeutic strategy in neuroinflammatory disorders.