Introduction

Mental illness such as mood disorders, schizophrenia and drug addiction is one of the most prevalent diseases in modern human society. However, the molecular mechanisms underlying pathogenesis of those diseases are largely unknown. Recently, the Molecular Psychiatry - molecular neurobiological study of psychiatric disorders - has emerged as a promising research domain of the modern neuroscience, rendering a unique approach to further understanding the pathogenesis of various psychiatric disorders. The Laboratory of Molecular NeuroPsychiatry (L.MNPSY) pursues in depth understanding of the molecular basis of psychiatric disorders, utilizing contemporary biochemical, molecular biological, cell biological, pharmacological, genetic and behavioral biological techniques. We believe that the research will not only expand our knowledge on higher brain functions such as cognition, emotion, mood, reward, and motivation but also allow identification of novel molecular targets for therapies against major psychiatric disorders

 

1. Modulation of dopamine receptor-mediated signaling and depression

Dopamine is one of the most functionally prevalent neurotransmitters in the vertebrate brain. Its role in higher brain functions is mediated by five subtypes of dopamine receptors. Among them dopamine D2 receptor (D2DR) has been implicated in various psychiatric diseases including attention deficit hyperactivity disorder (ADHD), mood disorders, schizophrenia and drug addiction. Thus detailed understanding of D2DR-mediated signaling mechanisms is thought to provide platform for elucidation of those related psychiatric problems. We are attempting to identify modulatory components in D2DR-mediated signaling in the context of higher brain functions and the pathogenesis of associated disorders.

 

2. Dopamine signaling and depression

Par-4 is a modulator of D2DR-mediated signaling. As a disruption of the normal function of Par-4 is associated with depression-like behaviors in a mouse model, it is thought to play a significant role in the pathways linking dopamine signaling and normal mood control. My group pursues further understanding of the neural function of Par-4 in relation to mood disorders, evaluating potentials as a molecular target for novel anti-depression therapies.

 

3. Molecular modeling of schizophrenia

Schizophrenia is a psychiatric disorder that is thought to have both neurochemical aspects (imbalances in dopamine, glutamate and GABA neurotransmission) and neurodevelopmental aspects (neuronal positioning, neuronal polarity and neurite outgrowth) in its pathogenesis. The complexity of the pathogenesis has hindered establishment of the genuine animal model reflecting schizophrenic condition. Recently, advances in human genetics provided candidates genes causative in the expression of schizophrenia. We attempt to understand their physiological function to establish animal models useful to elucidate the molecular basis of schizophrenia.