Application of stem cell therapies and assessment of motor and non-motor changes in a rat parkinson model

• Author(s): Carvalho, Miguel Maria Vinha Murteira de
• Date: 2009
• Persistent ID: http://hdl.handle.net/10451/1453
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Biologia celular; Células estaminais; Doença de Parkinson; Teses de mestrado
• Document Type: Master thesis
• Language: English
• Advisor(s): Salgado, António,; Rodrigues, Maria Gabriela
• Contributor(s): Repositório da Universidade de Lisboa

Description

Tese de mestrado, Biologia (Biologia Evolutiva e do Desenvolvimento), 2009, Universidade de Lisboa, Faculdade de Ciências

Resumo alargado disponível em português

Parkinson's disease is currently the most common motor disorder afflicting aged people. Described in 1817 by James Parkinson, this neurodegenerative disease is characterized by a progressive neuronal death in the dopaminergic system, being particularly severe in the substantia nigra pars compacta. Such degeneration has a negative impact upon neuronal circuits involved in motor execution, cognitive function and emotional homeostasis. It is thus of the utmost importance the development of effective treatments. However, the current treatment options are unsuccessful in stopping or even slowing down the progressive degeneration of the dopaminergic system. The discovery of stem cells brought a new hope to the field, since their remarkable potential to proliferate and differentiate into several cell types can be used, in theory, to replenish the dopaminergic populations lost. In this study the therapeutical potential of human umbilical cord perivascular cells (HUCPVCs), and their conditioned medium (CM), was assessed in an animal model of PD. The impact of HUCPVCs and their CM on the activity of the dopaminergic system and motor performance was assessed through the apomorphine-induced rotatory behavior and the rotarod test, respectively. Both cells and CM showed ameliorative action regarding dopaminergic function. However these results were not paralleled by significant improvements in motor performance. A second objective of this study was to perform a thorough behavioral analysis of a unilaterally 6-hydroxydopamine-injected rat model of PD. The availability of PD animal models, reproducing the major hallmarks of the disease, is crucial to the field, not only to better comprehend the multiple pathological events of PD, but also to test new treatments. In that sense, the described model was characterized regarding motor, cognitive and emotional aspects of its behavior. The results showed that this model presents clear motor impairments along with cognitive and emotional alterations.