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Researchers from Coimbra create innovative model in the study of autism

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A team of researchers from the Center for Neuroscience and Cell Biology (CNC) of the University of Coimbra has developed, in collaboration with researchers from the Massachusetts Institute of Technology, a new animal model to study autism. This work was recently published in the scientific journal Nature Communications.

Characterized by stereotypes (repetitive actions), changes in language and social behaviours, the spectrum of autism is a neurological disorder usually caused by mutations of different genes, which result in distinct forms of the disease. However, there are some changes common to various forms of autism, such as modifications in the metabotropic receptors of glutamate, a specific set of receptors of neurons: it is in the study of these receptors that the work of the CNC-UC team has achieved a significant advance.

With this study, we intend to have a deeper understanding of certain important aspects of the autism pathology. Our work is the first to look at the GPRASP2 gene in detail. We think this is an interesting target because it can be used in the regulation of multiple forms of this disease, “says João Pessoa, leader of the research team.

The study, published in the journal Nature, has shown in mice that the removal of the GPRASP2 gene – which recycles metabotropic receptors during neuronal communication – affects brain function and animal behaviour. Through genetic engineering, it has been proven that this recycling function is extremely important because in its absence there is less maturation of neurons during brain development – particularly in the hippocampus region, the brain zone that enables learning and the formation of new memoirs.

The new issues we are working on understanding a little better than other areas of the brain and what cell types are actually responsible for the various dysfunctions we observe in animals with mutations in the GPRASP2 gene. In this way, we will also realize which circuits we can modulate with alterations in this gene. For example, we wonder if the changes in the social behaviours of animals will not be due to changes in the hypothalamus, another region where there is a great expression of this gene, “says João. “It motivates us to understand if a future therapy that regulates the levels of GPRASP2 could be used in forms of autism where there is a disturbance of the metabotropic receptors. Therefore, the study is a seed for future projects, “concludes the CNC Researcher.

This study – which, in addition to Joao Pessoa, features Mohamed Edfawy as lead author and with Joana Guedes, Marta Pereira, Mariana Laranjo, Mário Carvalho, Pedro Ferreira, Gladys Caldeira, Lara Franco, Ana Luísa Cardoso and Ana Luísa Carvalho as co was funded by the Foundation for Science and Technology, the Bial Foundation, the Brain & Behavior Research Foundation (US) and supported by the European project ‘Marie Curie’. The article ‘Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice’ can be read in full here.

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