Regulatory role of BDNF on emotional and cognitive function

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H03123
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Keio University
• Principal Investigator: Kenji Tanaka 慶應義塾大学, 医学部(信濃町), 准教授 (30329700)
• Research Collaborator: SUZUKI Toru
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: BDNF / うつ病 / 多機能遺伝子改変 / 肥満

Outline of Final Research Achievements

It is well accepted that brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity. Human studies demonstrated that serum BDNF amount can be used as a biomarker of neuropsychiatric conditions. However, how BDNF directly regulates brain higher functions is still unknown. Here we developed BDNF gene modifying mice in which BDNF gene expression was capable of time- and region-dependent manipulation. In the stress-free condition, up- or down-regulation of BDNF gene expression did not cause any anxiety-like and depression-like behaviors.In the stressful condition, down-regulation of BDNF gene expression impaired the autonomic function characterized with basal tear secretion. In particular, down-regulation of BDNF expression delayed a recovery from the stress. We conclude that levels of BDNF expression affect the stress resilience in stressful condition but not in stress free condition.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

うつ病のバイオマーカーとして血液中のBDNF量が注目されている。これまでは、うつ病の診断基準を満たすかどうかで疾患群と健常群を分けて解析されてきた。今回の研究から、BDNFはうつ病の直接的な原因というよりも、ストレス応答にかかわる分子であることが示唆された。それにより、ヒトにおいて高ストレス状態・低ストレス状態の分類や、ストレスレジリエント・ストレス脆弱の分類を設けて、BDNF量を解析することを提案できる。うつ病のかかりやすさや初期症状をストレス応答で切り分ける研究へと展開することが期待できる。