Epigenetics Provide Further Support for the Psychosomatic Medical Study

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  • Takeda Hiroshi
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Miyagawa Kazuya
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
  • Tsuji Minoru
    Department of Pharmacology, School of Pharmacy, International University of Health and Welfare

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Other Title
  • エピジェネティクスが拓く新たな心身医学研究
  • 教育講演 エピジェネティクスが拓く新たな心身医学研究
  • キョウイク コウエン エピジェネティクス ガ ヒラク アラタ ナ シンシン イガク ケンキュウ

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Abstract

Recent research has demonstrated that complex ‘epigenetic’ mechanisms, which regulate gene transcription without altering the DNA code, could play a critical role in the pathophysiology of psychiatric disorders. The present review summarizes recent evidence for the existence of sustained epigenetic mechanisms of gene regulation in several psychiatric disorders such as depression, schizophrenia and Rett syndrome. The gene transcriptions of the key molecules such as brain-derived neurotrophic factor (BDNF) or reelin that play a role in on psychiatric disorders are regulated with histone modification or DNA methylation. Furthermore, one potential mechanism whereby stress can disrupt prenatal and/or neonatal development is through epigenetics, because the key issue of epigenetics is its long-term influence. The present review also focuses on the roles of brain 5-HT1A receptor-mediated epigenetic mechanisms in the development of resistance to emotional stress. Behavioral pharmacological studies have demonstrated that treatment with a 5-HT1A receptor agonist 24 h before testing suppressed the decrease in emotional behaviors induced by acute restraint stress. Studies with DNA microarray technology have revealed that histone deacetylase genes decreased in the hippocampus of mice that had been pretreated with a 5-HT1A receptor agonist 24 h beforehand. In addition, we found that acetylated histone H3 increased. Interestingly, similar to a 5-HT1A receptor agonist, the histone deacetylase inhibitor trichostatin A also protected against the emotional changes induced by acute restraint stress, as well as histone H3 acetylation. The present findings suggest that the epigenetic mechanisms of gene regulation may play an important role in the development of emotional resistance to stress stimuli. A better understanding of epigenetic regulation might provide new therapeutic avenues for disorders such as depression, schizophrenia, Rett syndrome and neurodevelopmental diseases.

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