Inflammatory response of the habenula underlying depressive-like behaviors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02581
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Hiroshima University
• Principal Investigator: Aizawa Hidenori 広島大学, 医系科学研究科(医), 教授 (80391837)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: うつ病 / 手綱核 / モノアミン

Outline of Final Research Achievements

We activated the mouse habenula via chemogenetic probe and observed depressive-like reduction of the locomotor activity in the home cage and inflammatory changes in gene expression pattern. This indicated the possibility that neuronal activation led to the local inflammatory response in the habenula. We also revealed that astrocytic activation and lipopolysaccharide activated the habenular neurons via increased extracellular potassium ion in mouse. In the way of the above analyses, we published 5 articles in the international academic journals by developing a novel equipment useful for mouse behavioral analysis, unraveling evolutionarily conserved mechanism of neuroinflammation and consequences of the systemic inflammation in brain function.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、近年うつ病の責任病巣の候補として注目される手綱核の機能を明らかにするもので、多様な症状から画一的な診断・治療法開発が困難であったうつ病の層別化と新たな病態仮説を提供する点で社会的意義が大きい。また、うつ病の病態には神経伝達物質の代謝や神経新生、炎症反応など様々な仮説が混在しており、統一的な見解が得られていない。本研究の成果では、モノアミンとよばれる神経伝達物質の制御にあたる手綱核の炎症反応機構を明らかにするもので、長い歴史をもつモノアミン仮説と近年注目を集める神経炎症仮説の発展的統合を目指す点で学術的にも重要なものと考えられる。