Expressão de miRNAS em PBMCS de indivíduos autistas e seus pais
Data
2024-08-13
Autores
Manzini, Camila Estevam 
Orientadores
Teixeira, Taiza Stumpp
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O autismo, referido como transtorno do espectro autista, é um transtorno complexo do neurodesenvolvimento que possui alta herdabilidade. Além da predisposição genética, os aspectos epigenéticos parecem estar envolvidos nessa condição. Embora estudos sugiram alteração da expressão de miRNAs em diferentes amostras de pessoas autistas, os dados ainda são bastante controversos. A influência ambiental é fundamental para o desenvolvimento dos autismos e a epigenética é referida como a forma pela qual o ambiente é biologicamente incorporado. Assim, sugere-se que essa influência epigenética também tenha papel na herança paterna do autismo. Objetivos: Investigar possíveis alterações na expressão de miRNAs em PBMCs de participantes com autismo e seus pais. Métodos: Foi coletado sangue de participantes com diagnóstico clínico de autismo (n = 20), de seus pais (n = 19) e de pessoas não autistas (controles; n = 14). Os miRNAs foram extraídos das células mononucleares de sangue periférico (PBMC) para investigação da expressão de alvos específicos (miR-18a-5p, miR-23a-5p, miR-34a-5p, miR-132-5p, miR-146a-5p, miR-195-5p e miR-484) via RT-qPCR. Resultados: Foi observada alteração estatisticamente significante na expressão dos miRNAs miR-18a-5p, miR-23a-5p e miR-146a-5p entre os grupos PAI e controle, mas não entre o grupo TEA e o controle. A análise bioinformática mostrou que esses miRNAs regulam genes envolvidos no neurodesenvolvimento e na resposta inflamatória. Conclusões: Os resultados sugerem que os miRNAs relacionados com o neurodesenvolvimento e inflamação estão alterados em pais de pessoas autistas, de modo que se pode inferir que essa alteração tenha papel na herança do autismo.
Autism, referred to as autism spectrum disorder (ASD), is a complex neurodevelopmental disorder with a high degree of heritability. In addition to genetic predisposition, epigenetic factors appear to play a role in this condition. Although studies suggest alterations in the expression of miRNAs in different samples from autistic individuals, the data remains highly controversial. Environmental influence is crucial for the development of autism, with epigenetics described as the means through which the environment is biologically embedded; it is suggested that this epigenetic influence also plays a role in the paternal inheritance of autism. Objectives: To investigate potential alterations in miRNA expression in PBMCs of participants with autism and their fathers. Methods: Blood was collected from participants clinically diagnosed with autism (n = 20), their fathers (n = 19), and nonautistic individuals (controls; n = 14). miRNAs were extracted from PBMCs to investigate specific targets (miR18a5p, miR23a5p, miR34a5p, miR1325p, miR146a5p, miR1955p, and miR484) using RTqPCR. Results: Statistically significant alterations were observed in the expression of miRNAs miR18a5p, miR23a5p, and miR146a5p between the fathers and controls, but not between the ASD group and controls. Bioinformatics analysis indicated that these miRNAs regulate genes involved in neurodevelopment and inflammatory response. Conclusions: The results suggest that miRNAs related to neurodevelopment and inflammation are altered in fathers of autistic individuals, implying a potential role in the inheritance of autism.
Autism, referred to as autism spectrum disorder (ASD), is a complex neurodevelopmental disorder with a high degree of heritability. In addition to genetic predisposition, epigenetic factors appear to play a role in this condition. Although studies suggest alterations in the expression of miRNAs in different samples from autistic individuals, the data remains highly controversial. Environmental influence is crucial for the development of autism, with epigenetics described as the means through which the environment is biologically embedded; it is suggested that this epigenetic influence also plays a role in the paternal inheritance of autism. Objectives: To investigate potential alterations in miRNA expression in PBMCs of participants with autism and their fathers. Methods: Blood was collected from participants clinically diagnosed with autism (n = 20), their fathers (n = 19), and nonautistic individuals (controls; n = 14). miRNAs were extracted from PBMCs to investigate specific targets (miR18a5p, miR23a5p, miR34a5p, miR1325p, miR146a5p, miR1955p, and miR484) using RTqPCR. Results: Statistically significant alterations were observed in the expression of miRNAs miR18a5p, miR23a5p, and miR146a5p between the fathers and controls, but not between the ASD group and controls. Bioinformatics analysis indicated that these miRNAs regulate genes involved in neurodevelopment and inflammatory response. Conclusions: The results suggest that miRNAs related to neurodevelopment and inflammation are altered in fathers of autistic individuals, implying a potential role in the inheritance of autism.
Descrição
Citação
MANZINI, Camila Estevam. Expressão de miRNAS em PBMCS de indivíduos autistas e seus pais. 130 f. 2024. Dissertação (Mestrado em Biologia Estrutural e Funcional) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2024.