Administração de ômega 3 em culturas de células neuronais (NEURO 2a): estudo da via de diferenciação celular NOTCH
Data
2023-04-26
Autores
Reis, Henrique Nogueira 
Orientadores
Silva, Cristiano Mendes da
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O ômega 3 é uma família de ácidos graxos formados pelos ácidos graxos essenciais, entre eles estão o ácido alfa linolênico (ALA), ácido eicosapentaenoico (EPA) e o ácido docosahexaenóico (DHA). O DHA auxilia na neurogênese, sugerindo que ele possui a propriedade de modular a função hipocampal regulada pela neurogênese com a promoção da diferenciação celular de células tronco em células neuronais maduras. A ativação da sinalização de Notch induz a expressão de genes repressores da transcrição, como o Hes1 e Hes5, levando à repressão da expressão do gene proneural e à manutenção de células-tronco/progenitoras neurais. O acréscimo de DHA para a promoção do crescimento e diferenciação neuronal, inclusive de oligodentritos, sugere um aumento significante da expressão de Notch1 e Hes1. Este estudo teve por objetivo avaliar in vitro, a via de sinalização celular Notch em linhagem celular de neuroblastos (células Neuro-2a) tratada com ácidos graxos ômega 3, e consequentemente averiguar inter-relação destes fatores com a neurogênese. Os experimentos in vitro foram realizados em culturas derivadas de neuroblastos e tratadas com um composto de ômega 3, rico em DHA durante 36h na concentração de 50μM e 100μM (DHA). Os resultados da expressão proteica de HES5 não apresentaram diferneça significativa, já a expressão de NOTCH1 e MASH1 tiveram uma significante diferença, principalmente nos tratamentos do grupo inflamado com LPS e adicionado 50μM e 100μM (DHA) (p=0,001). A inativação da família NOTCH/HES e seus genes relacionados regulam positivamente a expressão de MASH1 e aumentam a neurogênese. Considera-se que as célular Neuro-2a tratadas com o composto de ômega 3 apresentaram a sinalização celular da via NOTCH, aumentando a expressão de MASH1 e suprimindo a expressão de HES5 quando estimuladas a um ambiente de inflamação e tratamento com o composto a uma concentração de 100 μM de DHA.
Omega 3 is a family of fatty acids formed by essential fatty acids, including alpha linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA aids in neurogenesis, suggesting that it has the property of modulating neurogenesis-regulated hippocampal function by promoting stem cell differentiation into mature neuronal cells. Activation of Notch signaling induces expression of transcriptional repressor genes such as Hes1 and Hes5, leading to repression of proneural gene expression and maintenance of neural stem/progenitor cells. The addition of DHA to promote neuronal growth and differentiation, including oligodendrites, suggests a significant increase in Notch1 and Hes1 expression. This study aimed to evaluate, in vitro, the Notch cell signaling pathway in a neuroblast cell line (Neuro-2a cells) treated with omega 3 fatty acids, and consequently to ascertain the interrelationship of these factors with neurogenesis. The in vitro experiments were carried out in cultures derived from neuroblasts and treated with an omega 3 compound, rich in DHA, for 36h at a concentration of 50μM and 100μM (DHA). The results of HES5 protein expression showed no significant difference, whereas the expression of NOTCH1 and MASH1 had a significant difference, especially in the treatments of the inflamed group with LPS and added 50μM and 100μM (DHA) (p=0.001). Inactivation of the NOTCH/HES family and its related genes upregulates MASH1 expression and enhances neurogenesis. It is considered that Neuro-2a cells treated with the omega 3 compound showed the NOTCH pathway cell signaling, increasing the expression of MASH1 and suppressing the expression of HES5 when stimulated to an enviroμMent of inflammation and treatment with the compound at a concentration of 100 µM DHA.
Omega 3 is a family of fatty acids formed by essential fatty acids, including alpha linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA aids in neurogenesis, suggesting that it has the property of modulating neurogenesis-regulated hippocampal function by promoting stem cell differentiation into mature neuronal cells. Activation of Notch signaling induces expression of transcriptional repressor genes such as Hes1 and Hes5, leading to repression of proneural gene expression and maintenance of neural stem/progenitor cells. The addition of DHA to promote neuronal growth and differentiation, including oligodendrites, suggests a significant increase in Notch1 and Hes1 expression. This study aimed to evaluate, in vitro, the Notch cell signaling pathway in a neuroblast cell line (Neuro-2a cells) treated with omega 3 fatty acids, and consequently to ascertain the interrelationship of these factors with neurogenesis. The in vitro experiments were carried out in cultures derived from neuroblasts and treated with an omega 3 compound, rich in DHA, for 36h at a concentration of 50μM and 100μM (DHA). The results of HES5 protein expression showed no significant difference, whereas the expression of NOTCH1 and MASH1 had a significant difference, especially in the treatments of the inflamed group with LPS and added 50μM and 100μM (DHA) (p=0.001). Inactivation of the NOTCH/HES family and its related genes upregulates MASH1 expression and enhances neurogenesis. It is considered that Neuro-2a cells treated with the omega 3 compound showed the NOTCH pathway cell signaling, increasing the expression of MASH1 and suppressing the expression of HES5 when stimulated to an enviroμMent of inflammation and treatment with the compound at a concentration of 100 µM DHA.
Descrição
Citação
REIS, Henrique Nogueira. Administração de ômega 3 em culturas de células neuronais (NEURO 2a): estudo da via de diferenciação celular NOTCH. 2023. 42 f. Dissertação (Mestrado Interdisciplinar em Ciências da Saúde) - Universidade Federal de São Paulo, Instituto de Saúde e Sociedade, Santos, 2023.