Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model of Parkinson's disease

• Autor(a) principal: Esteves, Marta Raquel Carrola
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/3237
• topic: Doença de Parkinson - Ácido retinóico; Neurónios dopaminérgicos; Neuroprotecção - Nanopartículas; Nanopartículas

Retinoic acid (RA) plays an important role in the developing mammalian nervous system and has been highlighted as a therapeutic option for some neurodegenerative diseases due to its neuroprotective, anti-inflammatory and pro-neurogenic properties. However, RA presents undesirable properties like poor water solubility and short half-life. Therefore, nanoparticles (NPs) are an excellent alternative to control the undesired side effects and to ensure intracellular transport and controlled release of RA. Thus, the aim of this work was to evaluate the effects of RA-loaded NPs (RA+-NPs) in an in vivo mouse model of Parkinson’s disease (PD) using a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxin, and to compare with effects of soluble RA. Interestingly, in adult mice, RA+-NPs significantly reduced the MPTP lesion by increasing the percentage of tyrosine hydroxylase positive (TH+) dopaminergic neurons in the SN to levels similar to control as well as increasing the intensity and area occupied by TH+ fibers in the striatum. This protective effect mediated by RA+-NPs was more robust than when compared with effect of soluble RA. These effects were accompanied by an increase in mRNA expression in SN and striatum of Nurr1 and Pitx3, both transcription factors involved in dopaminergic survival and specification. The same pattern of Pitx3 mRNA expression was found in the SN of old mice. In conclusion, RA+-NPs show a robust protective effect against dopaminergic injury when compared to soluble RA, suggesting that RA+-NPs could be a good strategy to boost brain repair in PD.