Dissociação entre a resposta dopaminérgica e a função motora promovida pelo transplante intracerebral, mas não intravenoso, de células mononucleares da medula óssea em modelo lesional da doença de Parkinson

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Silva, Caroline Calice da lattes
Orientador(a): Costa, Jaderson Costa da
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
Programa de Pós-Graduação: Programa de Pós-Graduação em Medicina e Ciências da Saúde
Departamento: Faculdade de Medicina
País: Brasil
Palavras-chave em Português:
Área do conhecimento CNPq:
Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/6200
Resumo: Parkinson’s disease is characterized by the progressive loss of dopaminergic neurons from the substantia nigra, a process that leads to a dopamine deficiency in the striatum. This deficiency is responsible for the development of motor symptoms, including resting tremor, bradykinesia, rigidity and postural instability. New alternatives to Parkinson’s disease treatment have been studied, including cell-based therapies. The present study aimed to assess the therapeutic potential of intravenous and intrastriatal transplant of bone marrow mononuclear cells in a mouse model of Parkinson’s disease. Animals underwent stereotaxic surgery and 1μl of 6-hidroxidopamine (6-OHDA) was injected into their medial forebrain bundle. Two weeks later, mice were evaluated in the apomorphine rotation test to confirm the model induction. In the next week, animals’ pre-transplant motor function was assessed by Rotarod test. Then, BMMC or saline injection was carried out through the tail vein or directly into animals’ striatum. Motor function was also assessed using the Rotarod and apomorphineinduced rotation tests, 10 and 30 days post-transplant.Our results showed that intravenous BMMC did not restore the motor function in PD mice. In addition, transplanted cells were found only 24h after transplant in the brain tissue. On the other hand, the BMMC intracerebral transplant prevented the dopaminergic deficit progress, induced by 6-OHDA injection, effect seen in apomorphine-induced rotation test, only 10 days post-transplant. This potential was not seen on Rotarod test, showing dissociation between dopaminergic response and motor function. In addition, it was carried out a BMMC double transplant into parkinsonian mice’s striatum. It was shown, however, an increase in the apomorphineinduced rotations number, 30 days after the first transplant, even after a second injection of BMMC at 20 days. It was also shown, that, BMMC can be detected for at least 30 days after the intrastriatal transplant. Further experiments are needed to elucidate the mechanisms involved in these effects.