Os distúrbios comportamentais observados no autismo estão associados a uma multiplicidade de alterações genéticas. Cientistas do Hector Institute for Translational Brain Research (HITBR) encontraram outra causa molecular para essa condição.
![](data:image/jpeg;base64,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)
Pixabay
Os distúrbios comportamentais observados no autismo estão associados a uma multiplicidade de alterações genéticas. Cientistas do Hector Institute for Translational Brain Research (HITBR) encontraram outra causa molecular para essa condição.
O fator de transcrição MYT1L normalmente protege a identidade molecular das células nervosas . Se ele for geneticamente desativado em células nervosas humanas ou em camundongos, ocorrem as alterações funcionais e os sintomas típicos do autismo. Uma droga que bloqueia os canais de sódio na membrana celular pode reverter as consequências da falha do MYT1L e aliviar as anormalidades funcionais e comportamentais em camundongos.
Os distúrbios do espectro do autismo (TEA, transtornos do espectro do autismo ) não se manifestam apenas por deficiências na interação social, comunicação, formação de interesse e por padrões de comportamento estereotipados, mas são frequentemente acompanhados por outras anormalidades, como epilepsia ou hiperatividade.
Os cientistas estão procurando atentamente as anormalidades moleculares que contribuem para esse complexo distúrbio do desenvolvimento. Uma infinidade de fatores genéticos que influenciam os programas moleculares das células nervosas já foram associados ao desenvolvimento do autismo.
Moritz Mall, do Hector Institute for Translational Brain Research (HITBR), há muito pesquisa o papel da proteína MYT1L em várias doenças neuronais. A proteína é um chamado fator de transcrição que decide quais genes são ativos na célula e quais não são. Quase todas as células nervosas do corpo produzem MYT1L durante toda a sua vida.
Mall já havia mostrado há alguns anos que o MYT1L protege a identidade das células nervosas suprimindo outras vias de desenvolvimento que programam uma célula em direção ao músculo ou ao tecido conjuntivo, por exemplo. Mutações no MYT1L foram encontradas em várias doenças neurológicas, como esquizofrenia e epilepsia, mas também em malformações cerebrais. Em seu trabalho atual, Mall e sua equipe examinaram o papel exato do "guardião da identidade neuronal" no desenvolvimento de um TEA. Para fazer isso, eles desligaram geneticamente o MYT1L – tanto em camundongos quanto em células nervosas humanas derivadas de células-tronco reprogramadas em laboratório.
A perda de MYT1L levou à hiperativação eletrofisiológica em neurônios de camundongos e humanos e, portanto, prejudicou a função nervosa. Camundongos sem MYT1L sofriam de anormalidades cerebrais, como um córtex cerebral mais fino. Os animais também mostraram várias mudanças comportamentais típicas do ASS, como déficits sociais ou hiperatividade.
O que foi particularmente impressionante sobre os neurônios com deficiência de MYT1L: eles produziram um excesso de canais de sódio que normalmente são restritos principalmente às células do músculo cardíaco. Essas proteínas em forma de poro permitem que os íons de sódio passem através da membrana celular e, portanto, são cruciais para a condutividade elétrica e, portanto, também para o funcionamento das células. Se uma célula nervosa produz muitas dessas proteínas de canal, a hiperativação eletrofisiológica pode ser o resultado.
Na medicina clínica, drogas que bloqueiam os canais de sódio são usadas há muito tempo. Estes incluem o agente lamotrigina, que supostamente previne ataques epilépticos. Quando células nervosas com deficiência de MYT1L foram tratadas com lamotrigina , sua atividade eletrofisiológica voltou ao normal. Em camundongos, a droga foi até capaz de conter comportamentos associados ao TEA, como hiperatividade.
"Aparentemente, o tratamento medicamentoso na idade adulta pode aliviar a disfunção das células cerebrais e, assim, neutralizar as anormalidades comportamentais típicas do autismo - mesmo depois que a ausência de MYT1L já prejudicou o desenvolvimento do cérebro durante a fase de desenvolvimento do organismo", explica Moritz Mall. No entanto, os resultados ainda são limitados a estudos em camundongos; estudos clínicos em pacientes com transtornos do espectro do TEA ainda não foram conduzidos. Os primeiros estudos clínicos estão na fase inicial de planejamento.
O estudo foi publicado na revista Molecular Psychiatry .
Mais informações: Bettina Weigel et al. A haploinsuficiência de MYT1L em neurônios humanos e camundongos causa fenótipos associados ao autismo que podem ser revertidos por intervenção genética e farmacológica, Molecular Psychiatry (2023). DOI: 10.1038/s41380-023-01959-7
Informações do periódico: Molecular Psychiatry