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Finding new secretomes for Parkinson's disease regenerative medicine applications

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Resumo:Parkinson’s Disease (PD) is a progressive neurodegenerative disease that is primarily characterized by the loss of dopaminergic neurons (DAn), mostly in the nigrostriatal pathway, leading to dopamine (DA) deficiency, thereby causing the appearance of the characteristic PD motor and non-motor symptoms. Current state of the art in the field is based on the use of pharmacotherapies. However, these just mitigate motor symptomatology instead of stoping/delaying the progression of the disease, whereby imposing an urgent need for innovative therapeutical approaches. Human Mesenchymal Stem Cells (hMSCs) secretome has been presented as a promising therapeutic option, given their ability to modulate DAn cell survival/differentiation. Apart from a direct effect in neuronal survival, recent studies showed the possibility of an interplay between hMSCs (secretome), glial cells and DAn. Indeed, glial cells have been regarded as potential targets and modulators of PD. Therefore, in the present thesis we aim to 1) determine the role of glial cells secretome and glial cells (preconditioned) with hMSCs secretome as modulators of in vitro neuronal survival and differentiation, and 2) investigate the effects of glial and hMSCs secretomes in a 6-hydroxydopamine (6-OHDA) rat model of PD. Our in vitro data revealed that hMSCs and glial cells secretome per se and glial cells (preconditioned with hMSCs secretome) secretome induced higher rates of neuronal differentiation. Curiously, in vivo, distinct effects between hMSCs and glial cells secretomes were observed. While hMSCs secretome induced a positive impact in the amelioration of PD motor symptoms (assessed by the rotarod and staircase tests), glial cells secretome had a more pronounced effect in ameliorating PD non-motor symptomatology, namely anxious and depressive-like behaviors. Overall, one can conclude that the use of different secretomes can differentially targets PD motor and non motor behavioral dimensions, thereby opening new avenues for the treatment of PD
Autores principais:Domingues, Ana Verónica Mendes
Assunto:Ciências Médicas
Ano:2018
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho

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