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Doctoral Thesis
DOI
10.11606/T.42.2014.tde-11032015-134512
Document
Author
Full name
Hadassa Batinga da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Torrão, Andréa da Silva (President)
Donato Júnior, José
Miranda Filho, Manoel de Arcisio
Viel, Tânia Araújo
Title in Portuguese
Participação do sistema canabinoide em processos oxidativo e inflamatório relacionados à neurodegeneração in vitro.
Keywords in Portuguese
Estresse oxidativo
Neuroproteção
Receptor CB1
Sistema endocanabinoide
Abstract in Portuguese
A ativação do receptor CB1, leva a modulação de processos intracelulares que muda a resposta celular de acordo com o estímulo, além de estar envolvida em mecanismos de proliferação, diferenciação, movimentação e morte celular. O objetivo desse trabalho foi avaliar a participação desse sistema em processos oxidativo e inflamatório relacionados à neurodegeneração in vitro. Foi utilizado a linhagem de neuroblastoma Neuro2a diferenciada em células dopaminérgicas que foram expostas a três condições: com 6OHDA, H2O2 e LPS e co-tratadas com o agonista do receptor CB1 ACEA e o antagonista/agonista inverso AM251 por 24 horas. Utilizamos parâmetros funcionais de viabilidade celular, produção de espécies reativas de oxigênio e técnica de western blot. O tratamento com ACEA ou ACEA/AM251 produziram um aumento da viabilidade celular nos três modelos de exposição propostos; redução da produção de espécies reativas de oxigênio e ativação da via da proteína ERK1/2, além da inibição da morte celular pela diminuição da expressão da caspase 3. Concluímos que os canabinoides escolhidos foram capazes de proteger as células dopaminérgicas do dano oxidativo e inflamatório através do aumento da sobrevida celular por diminuição da produção de ROS.
Title in English
Participation of the cannabinoid system in oxidative and inflammatory processes related to neurodegeneration in vitro.
Keywords in English
CB1 receptor
Endocannabinoid system
Neuroprotection
Oxidative stress
Abstract in English
The CB1 receptor activation leads to modulation of intracellular processes that change the cellular response according to the stimulus, as well as being involved in mechanisms of proliferation, differentiation, cell movement and death. The present study evaluated the participation of this system in oxidative and inflammatory processes related to neurodegeneration in vitro. We have used the Neuro2A neuroblastoma lineage, which those were differentiated into dopaminergic cells, and exposed to 6OHDA, H2O2 and LPS. They were co-treated with ACEA, CB1 receptor agonist, and AM251, the CB1 receptor antagonist/inverse agonist, for 24 hours. We used functional parameters of cell viability, production of reactive oxygen species and protein analyses by western blot. Treatment with ACEA or ACEA/AM251 produced an increase in cell viability; reduced production of reactive oxygen species and activation of the ERK1/2 protein, in addition to inhibition of cell death by decreasing the expression of caspase 3 in all three models proposed. We concluded that chosen cannabinoids were able to protect dopaminergic cells from oxidative damage and inflammation through the increased cell survival by decreasing the production of ROS.
 
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Release Date
2017-03-11
Publishing Date
2015-03-12
 
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