Department of Molecular & Cellular Physiology is focusing on the relevance between synaptic defect and the pathophysiology of neurodevelopmental disorders, such as autism.

　Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by impairments in social interaction, difficulties in verbal and non-verbal communication, and repetitive and restricted patterns of behavior. Recent reports indicate that ASD affects more than 1 out of 100 people, and symptoms typically manifest by the age of 3. However, diagnosing autism is not always straightforward, as some cases fall into a gray area and require monitoring until elementary school age when a definitive diagnosis can be made.

Autism and Genetic Abnormalities

　The cause of autism is primarily based on genetic background. However, this does not mean that autism is simply inherited from parents to children. Autism has been linked to a multitude of genes, each with various degrees of correlation. While an abnormality in a single gene with a strong correlation alone can lead to autism, a single abnormality in a gene with weak correlation does not cause autism. Many cases are caused by the presence of multiple genetic variants with weaker associations. Monozygotic twins have an identical gene sequence, meaning that their genetic makeup is exactly the same. Indeed the concordance rate of autism in monozygotic twins is high, but it is not 100%. There are cases where one twin is diagnosed with autism while the other is not. Furthermore, the severity or characteristics of symptoms can also be distinctive between monozygotic twins, even if both are diagnosed with autism. Given these facts, it can be inferred that environmental factors are also involved in the pathophysiology of autism. While environmental factors may contribute to the development of autism, genetic factors are considered the primary cause, and it is unlikely for environmental factors alone to lead to the disorder.

Pathology of Autism and Insight for Developing New Therapy

　In terms of the pathology of autism, a significant percentage of genes linked to the disorder are related to synapses, which are the sites for transmitting information across neurons. As a result, it has been suggested that synapse abnormalities may be at the core of autism's pathology. In particular, Neurexin and Neuroligin, two genes that encode molecules involved in connecting pre- and postsynapses, have been found to have a strong correlation with autism.

　In addition, studies have shown that the neural circuits in the medial prefrontal cortex, located in the frontal lobe of the cerebral cortex, are also related to the social abnormalities seen in autism. While autism is primarily based on genetic abnormalities, research using a mouse model of the disorder has shown that genetic manipulation in the neural circuits of the medial prefrontal cortex, even in adulthood, can reverse social deficits. This suggests that gene therapy may be a potential fundamental cure for autism.

　Overall, a better understanding of the pathophysiology of autism can lead to the development of new therapies for the disorder. While there is currently no cure for autism, ongoing research is providing valuable insights into the disorder's causes and potential treatments.

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