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Authors
Abstract(s)
A doença de Parkinson é uma doença neurodegenerativa causada pela perda de neurónios
dopaminérgicos. Tradicionalmente, têm sido utilizados animais vertebrados, maioritariamente
roedores, no estudo desta doença. Existem vários modelos disponíveis, incluindo o modelo com
o pesticida paraquato. No entanto, a experimentação animal com vertebrados tem sido objecto
de forte regulamentação, só sendo autorizada quando não existe alternativa não animal
disponível. Assim, o desenvolvimento e validação de modelos animais alternativos reveste-se
de particular importância. A Daphnia magna é um invertebrado aquático, que possui a
homologia genética mais elevada com o homem de entre os não vertebrados, e para a qual já
foi comprovada a existência de neurónios dopaminérgicos. No âmbito da presente tese, o
pesticida paraquato foi usado como substância modelo. Foram realizados testes agudos de
acordo com a norma 202 da OECD e foi avaliado o impacto na sobrevivência de Daphnia e em
termos de alterações de movimento. Os resultados obtidos demonstram que existe uma grande
variação nos valores de EC50 (Concentração responsável pela imobilização de 50% dos animais).
Essa variação foi atribuída à idade das Daphnia expostas. Apesar da norma da OCDE indicar que
os ensaios devem ser realizados com neonatos com menos de 24h, os resultados obtidos
demonstram claramente que esse intervalo deve ser reajustado uma vez que diferenças
relativamente reduzidas (i.e., duas horas) na idade dos neonatos são responsáveis por
diferenças nos valores de EC50. Relativamente às alterações no movimento foi possível observar
uma tendência de aumento no movimento (em termos de deslocamento) em função da idade
dos neonatos para a mesma concentração de paraquato. Foi ainda possível observar uma
diminuição no movimento com o aumento da concentração de paraquato para neonatos com a
mesma idade.
De uma forma geral, este trabalho demonstrou a Daphnia magna apresenta várias
características que a tornam um bom modelo para o estudo da doença de Parkinson, no entanto,
é necessário um ajuste ao protocolo da OECD e são necessários mais estudos particularmente
em termos de alterações de movimento.
Parkinson disease is a neurodegenerative disease caused by the loss of dopaminergic neurons. Traditionally, vertebrate animals, mostly rodents, have been used to study this disease. There are several models available, including the model with the pesticide paraquat. However, animal experimentation with vertebrates has growingly been regulated, only being authorized when no other alternative is available. Therefore, the development and validation of animal alternative models are of a particular significance. Daphnia magma is an aquatic invertebrate, that has the highest genetic homology with humans among non vertebrates, and for which it has been verified the existence of dopaminergic neurons. In this thesis, the pesticide paraquat had been used as model substance. Acute toxicity tests were performed according to the guideline 202 of OECD and the impact in the survival and motion changes of Daphnia were evaluated. The results obtained demonstrate that the values of EC50 (Concentration responsible for the immobilization of 50% of the animals) vary widely. That variation was attributed to the age of the exposed Daphnia. Although the OECD guideline indicates that the assays must be performed with neonates younger than 24 hours, our results clearly demonstrate that this age range should be narrowed since comparatively small variations (i.e., two hours) in the age of the newborns is responsible for differences in EC50 values. Concerning alterations in movement, it was possible to observe that older Daphnia display higher levels of movement (in terms of displacement). It was also possible to observe that, for neonates with the same age, there was a reduction in movement with increasing concentrations of paraquat. In a general, this work demonstrates that Daphnia magma presents characteristics that makes it a good alternative animal model for the study of Parkinson disease. Although, it is required an adjustment to the OECD’s protocol and further research is necessary, particularly studies related with movement alterations.
Parkinson disease is a neurodegenerative disease caused by the loss of dopaminergic neurons. Traditionally, vertebrate animals, mostly rodents, have been used to study this disease. There are several models available, including the model with the pesticide paraquat. However, animal experimentation with vertebrates has growingly been regulated, only being authorized when no other alternative is available. Therefore, the development and validation of animal alternative models are of a particular significance. Daphnia magma is an aquatic invertebrate, that has the highest genetic homology with humans among non vertebrates, and for which it has been verified the existence of dopaminergic neurons. In this thesis, the pesticide paraquat had been used as model substance. Acute toxicity tests were performed according to the guideline 202 of OECD and the impact in the survival and motion changes of Daphnia were evaluated. The results obtained demonstrate that the values of EC50 (Concentration responsible for the immobilization of 50% of the animals) vary widely. That variation was attributed to the age of the exposed Daphnia. Although the OECD guideline indicates that the assays must be performed with neonates younger than 24 hours, our results clearly demonstrate that this age range should be narrowed since comparatively small variations (i.e., two hours) in the age of the newborns is responsible for differences in EC50 values. Concerning alterations in movement, it was possible to observe that older Daphnia display higher levels of movement (in terms of displacement). It was also possible to observe that, for neonates with the same age, there was a reduction in movement with increasing concentrations of paraquat. In a general, this work demonstrates that Daphnia magma presents characteristics that makes it a good alternative animal model for the study of Parkinson disease. Although, it is required an adjustment to the OECD’s protocol and further research is necessary, particularly studies related with movement alterations.
Description
Keywords
Animal Alternativo Daphnia Magna Doença de Parkinson Ocde Paraquato