Involvement of immune molecule MHC expressed in the brain in attention deficit/hyperactivity disorder

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: University of Miyazaki (2017-2018); Hamamatsu University School of Medicine (2015-2016)
• Principal Investigator: NAKAHARA Daiichiro 宮崎大学, 医学部, 研究員 (80128389)
• Co-Investigator(Kenkyū-buntansha): 村上 元 埼玉医科大学, 医学部, 講師 (70613727)
• Research Collaborator: SUENAGA Toshiko
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 主要組織適合遺伝子複合体 / 注意欠如・多動性障害 / 側坐核 / ドーパミン受容体 / メチルフェニデート

Outline of Final Research Achievements

Mice deficient in the function of major histocompatibility complex antigen class I (MHC-I) showed a human attention deficit/hyperactivity disorder-like phenotype, such as hyperactivity, motor impulsiveness, and inattention. In addition, expression of nucleus accumbens dopamine 1 receptor (D1R) was increased in MHC-I deficient mice. Administration of methylphenidate, a treatment for ADHD, to these mice ameliorated all symptoms of hyperactivity, impulsiveness and attention disorders. Furthermore, c-Fos expression of neurons with D1R in nucleus accumbens was significantly suppressed by methylphenidate.

Free Research Field

行動神経科学

Academic Significance and Societal Importance of the Research Achievements

MHC-I機能欠損マウスは、動物モデルとして、表面的妥当性、予測的妥当性、および構成的妥当性の３つの基準を概ね満たしており、長い間不明のままにあるADHDの病態メカニズムの解明に一歩近づくことが期待できる。