The work involved data from more than 900 children with ASD, as well as experiments with mini-brains derived from blood cells from volunteers.
A study conducted by Brazilian and North American scientists reveals that there is a relationship between the increase in size brain (macrocephaly) and increased severity of social and communication symptoms in children with autism spectrum disorder (ASD). The results have been published in the magazine Molecular autism.
The finding is based on the analysis of brain images of more than 900 children with ASD (conducted in the group’s previous work, from 2017) and also on recent experiments with mini brains: lab-grown organoids from blood cells differentiated into neurons from children who volunteered in the first study. In both cases, a relationship between macrocephaly and severity of symptoms was observed.
According to the newly published paper, mini-brains derived from cells from children with more severe symptoms were up to 41 percent larger than controls.
“Not all children with ASD and severe symptoms will have changes in brain size. However, when there is macrocephaly, the symptoms are more severe,” says Mirian Hayashi, professor of the Department of Pharmacology at the Escola Paulista de Medicina (EPM-Unifesp) and one of the main authors of the article.
This difference in brain size observed in the study volunteers appears to be linked to changes in the activity of an enzyme known as Ndel1. An equivalent phenomenon had already been identified by the Unifesp group in children with microcephaly induced by the Zika virus. Associated with several neurological disorders, such as schizophrenia, first-episode psychosis, and bipolar disorder, as well as congenital disorders zikaThis protein participates in the process of neuron migration during the formation of the brain in the embryonic stage.
As researchers believe, social and communication symptoms are common among individuals on the autism spectrum, but the severity varies from person to person.
Although the biological mechanism that determines the intensity of symptoms remains unknown, the findings of this research open new avenues for understanding ASD.
Methodology
The recently published work was divided into two phases. Initially, an analysis was carried out involving brain images and diagnostic data from over 900 children with ASD who are part of a cohort study coordinated by Eric Courchesne, a physician at the Autism Center of Excellence at the University of California, San Diego (USA).
Then, through studies conducted on mini-brains developed in the laboratory Alysson R. Muotriof the Department of Molecular and Cellular Medicine of the same university, it was possible to identify that, during the process of brain formation, problems related to cell migration and neuron formation are already present and can be evaluated, which could have an impact on brain size.
That’s because researchers were able to identify in the mini-brains that the protein Ndel1 plays an important role in cases of macrocephaly in children with ASD.
“It was already known that the neurons of people with autism showed changes. Analysis of mini-brains confirmed that, especially in cases of macrocephaly, there is an increase in the number of neural progenitors. [células que dão origem aos neurônios]. Our analysis showed that the brain is perhaps larger because of the high number of progenitor cells that are not able to differentiate during embryogenesis,” reports João Nani, who conducted the analyses at the Department of Molecular and Cellular Medicine at the University of California at San Diego with the support of Fapesp.
It was possible to observe that several neural cells did not function as they should, nor did they create connections (synapses) as expected. “The number of connections matters more than the number of neurons. That’s why having more neurons [caso da macrocefalia] much less [microcefalia] they are harmful,” explains Nani.
The researchers also measured the activity and expression of the enzyme Ndel1 in the mini-brains and found an imbalance in cases of macrocephaly.
“Ndel1 is an enzyme associated with the process of cell division and differentiation of neurons. Of course, these are processes that involve several other proteins, but most likely, in cases of macrocephaly, the entire system is out of balance and Ndel1 could be a biomarker that we found that this imbalance can lead to either an increase or a decrease in the brain. However, in the cases in which we evaluated, the mini-brains of peripheral blood mononuclear cells of children with autism and the severity of communication and social symptoms were increased,” says Nani.
The group now plans to conduct new studies aimed at identifying biomarkers related to disease severity in patients’ blood.
Source: Terra
Ben Stock is a lifestyle journalist and author at Gossipify. He writes about topics such as health, wellness, travel, food and home decor. He provides practical advice and inspiration to improve well-being, keeps readers up to date with latest lifestyle news and trends, known for his engaging writing style, in-depth analysis and unique perspectives.
