Principal Investigator_T.Takahashi
Post-translational modifications in mental disorder
Takuya Takahashi
Professor, Physiology
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Our Aim
Recent diagnosis and treatments of mental disorders remain poorly related to the molecular and cellular mechanisms underlying these diseases. The long term aim of our project is to establish novel diagnoses and treatments based on the molecular and cellular mechanisms of mental illnesses.
Background
Plasticity in our brain is required for the adaptation to novel environments. We hypothesize that the malfunctioning of the plasticity underscores the majority of mental disorders. For example, social anxiety disorder is considered to be the inability to adapt to the novel social environment, and this could be due to the disruption of neuronal plasticity. Thus, elucidation of the mechanisms underlying plasticity and its disruption in mental illness will lead to the establishment of novel diagnosis tools and medical treatments of mental disorders. Glutamatergic synapses are major excitatory synapses in the brain and essential for the processing of information. The glutamate AMPA receptor conveys information at these synapses. Synaptic trafficking of the AMPA receptor is a molecular and cellular mechanism underlying neural plasticity.
Research Overview
In this project, we aim to understand the molecular and cellular mechanisms underlying mental disorders by analyzing protein post-translational modifications with novel proteomics techniques.
Achievements
We found that the synaptic AMPA receptor delivery underlines neuronal plasticity in various environments. In particular, we found differences in AMPA receptor trafficking and its phosphorylation among enriched environments and abnormal social environments. Furthermore, we elucidated the role of the AMPA receptor on the formation of PTSD (post-traumatic stress disorder). These results led us to establish the novel concept of “AMPA receptor trafficking disorder” as a mechanism of mental disorders.