Alterations in Cell Environment Can Trigger Autism in the Genetically Susceptible

February 07, 2022

Study Provides More Evidence that Genes, Environment and Inflammation Are Tied to ASD

A breakthrough study developed from a team of researchers out of the University of Geneva (UNIGE), has demonstrated how a change in cell environment can trigger the development of autistic symptoms in mice with a genetic vulnerability. According to a News Medical article reporting on the study, the new research showed that “an imbalance in the expression of a series of genes caused by a massive inflammation – resulting from an immune response to the administration of a pharmacological product – leads to the hyperexcitability of neurons of the reward system.” The study’s authors came to this finding by examining heterozygous mice, i.e. mice carrying a deletion of only one of the two copies of the SHANK3 gene, but not exhibiting social behavioral disorders. The researchers then inhibited the expression of the SHANK3 in the neural networks of the reward system in order to identify the other genes whose expression became modified. Many genes related to the inflammatory system were discovered, including Trpv4, which plays a role in the communication channels between neurons. When massive inflammation was induced, the team observed an overexpression of Trpv4, which resulted in a neuronal hyperexcitability that accompanied the onset of social avoidance behaviors, which the mice previously did not exhibit. Furthermore, when the researchers inhibited the Trpv4 gene, the mice returned to exhibiting normal social behavior. The lead author, Camilla Bellone, believes that her study provides evidence that autism spectrum disorders are the result of an interaction between a genetic susceptibility and an external trigger, which in this case was massive inflammation. Additionally, she believes that neuronal hyperexcitability disrupts communication channels which alter the brain circuits that are responsible for social behavior. Her explanation also sheds light on why the same genetic predisposition can lead, depending on the environmental exposures and the type of inflammation triggered, to a wide spectrum of symptoms and varying levels of severity. Ultimately, this study highlights the need for understanding the mechanisms behind the development of autism in order to develop treatments that correspond specifically to the cellular and molecular modifications at stake in the brain circuits.

 

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