Scientists believe they have made a breakthrough in the understanding of the neuroscience behind autism spectrum disorders, with their findings focusing on the chemical dopamine which could change how treatment is approached, they said.
Autism spectrum disorders, the diverse group of conditions characterised by some degree of difficulty with social interaction and communication, affects about one in 100 children worldwide, but numerous questions still exist about the biochemical mechanisms underlying these.
Newsweek reports that there are various potential causes, with both environmental and genetic factors thought to play a role, but the latest evidence suggests that dopamine, the famous “feel-good” hormone, might play a leading role.
“While dopamine is commonly recognised as a neurotransmitter, its significance in the developmental aspects of autism is largely unexplored,” said lead investigators Lingyan Xing and Gang Chen of China’s Nantong University.
“Recent studies have highlighted the crucial roles of dopamine and serotonin in neurotypical brain development, and their importance in the construction of neural circuits. Additionally, studies have indicated that using dopamine-related drugs during pregnancy is associated with an increased risk of autism in children.
“Armed with these clues, we embarked on a mission to bridge the gap between dopamine’s known functions and its potential impact on neurodevelopmental disorders, particularly autism.”
In their study published in The American Journal of Pathology, the researchers describe investigating the role of dopamine signalling in autism development. “Our quest was to uncover a novel therapeutic target that could revolutionise how we approach autism treatment,” they said.
The study consisted of two parts. The first involved analysing changes in gene expression in the brains of people with autism. The second used zebra fish models to explore how perturbations in dopamine signalling could produce autism-like behaviours.
In the first part of the study, the team found that patients with autism showed changes in the expression of genes involved in dopamine-signalling pathways and brain development. The authors say this indicated a potential link between dopamine disruption and autism development.
To explore this link further, they re-created these disrupted dopamine pathways in the brains of zebra fish larvae and found that the larvae with signal disruption developed brain circuit abnormalities and behaviours reminiscent of human autism.
“We were surprised by the extent of the impact that dopaminergic signalling has on neuronal specification in zebra fish, potentially laying the groundwork for circuit disruption in autism-related phenotype,” Gang wrote.
Lingyan said this research sheds light on the role of dopamine in neural circuit formation during early development, specifically in the context of autism.
“Understanding these mechanisms could lead to novel therapeutic interventions targeting dopaminergic signalling pathways to improve outcomes in individuals with autism and other neurodevelopmental disorders.”
Study details
Developmental dopaminergic signalling modulates neural circuit formation and contributes to autism spectrum disorder–related phenotypes
Xiaojuan Lu, Yixing Song, Gang Chen et al.
Published in The American Journal of Pathology on 14 March 2024
Abstract
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with a complex etiology. Recent evidence suggests that dopamine plays a crucial role in neural development. However, whether and how disrupted dopaminergic signalling during development contributes to ASD remains unknown. In this study, human brain RNA sequencing transcriptome analysis revealed a significant correlation between changes in dopaminergic signalling pathways and neural developmental signalling in ASD patients. In the zebrafish model, disrupted developmental dopaminergic signalling led to neural circuit abnormalities and behaviour reminiscent of autism. Dopaminergic signalling may impact neuronal specification by potentially modulating integrins. These findings shed light on the mechanisms underlying the link between disrupted developmental dopamine signalling and ASD, and they point to the possibility of targeting dopaminergic signalling in early development for ASD treatment.
Newsweek article – New Autism Study Reveals 'Tantalizing Clues' About Its Development (Open access)
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