Role of microRNAs on glial activity in a Parkinson’s disease mouse model

• Autor(a) principal: Silva, Tânia Alexandra Salavessa
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/12897
• topic: Astrócitos; Doença de Parkinson; Microglia; Mir-204; Mir-224; Neuroinflamação; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Parkinson's disease (PD) is a neurodegenerative disease characterized by the accumulation of a-synuclein protein and, consequently, neuronal degeneration, culminating in motor and nonmotor symptoms. Its etiology may come from environmental agents or genetic factors. Currently, there are no effective treatments for PD, so it is important to identify new targets and therapeutic strategies. Experiments carried out in in vitro and in vivo animal models have been a valuable tool to understand the pathophysiological mechanisms of PD. Animal models allow the study of several characteristics of the PD phenotype and are categorized into genetic models and toxin-induced models, which include the model induced by 6- hydroxydopamine (6-OHDA) used in the present work. 6-OHDA is a neurotoxin that, after being taken up by dopaminergic neurons, through dopamine transporters (DAT), induces the formation of free radicals, mitochondrial dysfunction, and glial activation, culminating in the death of dopaminergic neurons. In different studies, miRNAs (miR) have been identified as attenuating PD due to their potent modulating effect on the regulation of gene expression associated with the pathophysiological mechanisms of PD. Previous studies by our research group showed that miR-124 has a neuroprotective and neurogenic effect in the 6-OHDA model. Other studies report increased levels of miR-204 and miR-224 in the brains of patients with PD and experimental cellular and animal models. Although there is evidence of increased values of these miRs, there are no studies on their cellular and molecular effects in PD models. In this study, we examined the effects of miR-204 and miR-224 on astrocytic and microglial activation, evaluating the protein expression levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (IBA-1) markers by western blot. As expected, we found an increase in GFAP and IBA-1 expression in the SN and SN of mice treated with 6-OHDA toxin compared to saline-treated mice, which indicates astrocytic and microglial activation, respectively. In animals exposed to 6-OHDA in the striatum and miR-204 or miR-224 in the substantia nigra, we observed a decrease in the expression of GFAP and IBA1 compared to animals treated with 6-OHDA, which suggests an anti-inflammatory and protective effects of these miRs. However, further studies are needed to better understand the effects of these miRs on PD, so that they can be used as therapeutic targets.