Activation of hippocampal protocadherin-MAP kinase cascade by the treatment of depression

2015 Fiscal Year Final Research Report

• Project/Area Number: 23590300
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Ritsumeikan University (2013-2015); Osaka University (2011-2012)
• Principal Investigator: Tanaka Hidekazu 立命館大学, 生命科学部, 教授 (70273638)
• Co-Investigator(Kenkyū-buntansha): YAMAGATA Kanato 公益財団法人・東京都医学総合研究所, シナプス可塑性プロジェクト, プロジェクトリーダー (20263262)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Keywords: 抗うつ薬 / シナプス可塑性 / 海馬 / プロトカドヘリン / マップキナーゼ / 接着分子 / 樹状突起スパイン

Outline of Final Research Achievements

Hippocampus, a part of the limbic system, shrinks in depressive patients. It is also reported that dendritic arbors shrink, and that the density of spines that form excitatory synapses decreases in hippocampus. All these parameters recover in individuals successfully treated with antidepressants. Arcadlin (or Protocadherin-8; Paraxial protocadherin) is a protocadherin-type cell adhesion molecule induced in hippocampal neurons by these treatments. Arcadlin is known to regulate spine density. The effect of antidepressants was rather enhanced in arcadlin-gene deleted mouse. The data suggest that Arcadlin is induced by antidepressants, but shows an antagonistic effect against the drug’s action.

Free Research Field

薬理学、神経化学