Noritaka ICHINOHE
Autism is a neurodevelopmental disorder characterized by difficulties in
social interaction, communication, and restricted and repetitive behaviors.
Core symptom onset occurs within the first three years of life, and its
incidence is estimated to be 1-2% worldwide. However, there is currently
no treatment for the core symptoms of autism.
Autism is thought to be caused by a combination of genetic and environmental
factors. Although several candidate genes have been identified, only about
15% of cases were found to be directly associated with genes linked to
autism symptoms. However, the relationship between idiopathic autism, which
accounts for the majority of autism cases (85%), and specific genes is
still not clearly understood. In addition to genetic factors, maternal
environmental factors also play a role in the onset of autism. For example,
infections or exposure of the epilepsy drug valproic acid during the mother’s
pregnancy may increase the risk of autism. These various factors are thought
to be intricately intertwined in causing the onset of autism.
Rodent (mouse and rat) models of autism have long been used to study the
pathogenesis of autism and for preclinical testing of therapeutic drug
candidates. However, in recent years, research using non-human primate
models of autism has emerged. Primates offer several advantages as a model
of autism. Primates, like humans, live in groups, and their lives require
social interaction skills, such as empathy, reciprocity, and the ability
to act appropriately in response to the actions of others. Impairment in
interaction is a major challenge for people with autism, and the primate
model may be useful in developing treatments for this problem. Further,
primates are evolutionarily closer to humans and have similarities in their
brain morphology, function, developmental processes, and gene co-expression
system.
Among primates, marmosets communicate richly using a variety of vocalizations.
They also form societies in which couples work together to raise their
children. In our laboratory, we developed the world's first model of autism
using marmosets by administering valproic acid to the mother during pregnancy.
This animal model replicates the difficulty autistic individuals have in
considering the behavior of others and performing their own actions appropriately.
Importantly, the synaptic and gene expression abnormalities in this marmoset
model were more similar to the data from the human autistic brain than
from popular rodent models. We are interactively analyzing this autism
marmoset model using molecular biological methods, behavioral analysis
methods, and morphological and functional analysis at the micro, meso,
and macro levels. We are also searching for biomarkers in tissues other
than the brain, such as blood. The search for biomarkers is important to
both aid in diagnosis and investigate new treatments. By combining these
methods, we are working toward the development of treatments that will
help people with autism.