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2023-09-05| R&D

Finding Hope in Autism Treatment Through Animal Models

by Sinead Huang
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Due to the lack of precise standards for individual cases, it has been challenging to conduct quantitative research and treatments for autism. A review article published in Molecular Psychiatry highlights that developing mouse models of human mental disorders has proven to be a viable approach for studying molecular mechanisms. Coupled with a previously developed virtual reality system, this sheds light on the latest advancements in autism research.

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Is autism diagnosable?

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by diminished social communication skills, intense obsessions with specific subjects, and repetitive behaviors. The number of individuals with autism continues to rise, making it a societal concern. As current autism diagnoses rely on behavioral characteristics, a lack of quantitative perspectives underscores the urgent need for new biomarkers to aid in diagnosis.

Experts continue to debate whether autism should be treated or approached with adaptive measures, reflecting the diversity of its manifestations and causes. This diversity, akin to a spectrum, complicates the study of autism’s mechanisms and the development of potential treatments in the absence of a quantitative assessment system or objective mechanized diagnostic methods.

Professor Toru Takumi from the Graduate School of Medicine at Kobe University explained, “Autism is a complex disease similar to cancer. While genetic factors play a more significant role in this disease compared to other mental disorders, environmental factors are also crucial. To treat autism, we need to understand the neural networks underlying social maladaptation and develop new techniques to manipulate human neural networks.”

Mouse Models Simulate Brain Mechanisms of Autism Patients

As a pioneer in developing mouse models of human mental disorders, Professor Takumi’s work with genetically modified mice exhibiting social behavioral disorders offers a unique opportunity to accurately analyze the molecular and physiological mechanisms behind autism. This work also provides a chance to test potential treatments. As an internationally recognized expert in the field, Professor Takumi was invited by Molecular Psychiatry to summarize the current research status.

In this review article, Professor Takumi emphasizes the significance of the insular cortex, which is deeply embedded in the brain and interconnected with sensory, emotional, motivational, and cognitive systems. In mice, this region is involved in regulating emotions, empathy, motivation, and other functions, whereas in humans, it relates to self-awareness. The review elaborates on the genes and physiological functions of the insular cortex that impact the emergence of autism. Professor Takumi explains, “Mental disorders are often viewed as disorders of neural circuits. Therefore, unraveling the workings of neural circuits responsible for social behavior will contribute to the development of future circuit-based therapies.”

New technologies for mouse brain

In recent years, research has been ongoing to uncover the specific brain functional abnormalities associated with autism. Functional magnetic resonance imaging (fMRI) studies under resting state conditions have shown increased brain network density in infantile autism patients, which decreases in adulthood. However, this variation exists significantly between individuals, and it remains unclear how these static brain network abnormalities affect behavior.

Given the close relationship between autism and genetic factors, genomic abnormalities such as copy number variations (CNV) are linked to brain neuropathology. To understand the neural pathology of autism, animal models that simulate human genomic abnormalities have been frequently employed.

Professor Takumi’s research team recently published in Cell Reports that they developed a virtual reality system capable of measuring widespread cortical neural activity in mice during their activities. This enables researchers to uncover anomalies in the cortical functional network dynamics of autism model mice. The cortex functional network in autism mice is dense and modularly reduced. Using machine learning, they were also able to accurately distinguish autism model mice from wild-type mice based on patterns of cortical network activity during running or resting.

Professor Takumi stated, “We are deeply interested in human cognition. By understanding the pathology and physiology of autism, I hope to understand how human thoughts are generated in the brain.” Through research, Professor Takumi seeks to comprehend the molecular basis of brain mental functions and, in the long run, contribute to autism diagnosis and treatment.

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