Study on the neural circuits that regulate feeding behavior by pathway-specific gene expression

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08526
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: National Institute for Physiological Sciences (2018); The University of Tokushima (2016-2017)
• Principal Investigator: Horio Shuhei 生理学研究所, 生体機能調節研究領域, 特別協力研究員 (80145010)
• Co-Investigator(Kenkyū-buntansha): 上山 敬司 和歌山県立医科大学, 医学部, 教授 (50264875) ; 井樋 慶一 東北大学, 情報科学研究科, 教授 (60232427)
• Research Collaborator: KOBAYASHI kazuto
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 摂食調節 / 視床下部 / 室傍核 / CRF / CRH / 弧束核 / 結合腕傍核 / 神経経路

Outline of Final Research Achievements

Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) are involved in many physiological functions. To study the role of CRH neurons, we classified PVH CRH neurons according to their differential projections to brain regions. First, we expressed GFP and wheat germ agglutinin(WGA) in CRH neurons; GFP was used for tracking neural pathways and WGA for the target neurons. Potential target regions were found to be the solitary nucleus, locus ceruleus, parabrachial nucleus, dorsal raphe, and lateral hypothalamus. Secondly, we used retrograde viral vector to selectively express GFP in the CRH neurons projecting to each site. The CRH neurons were distributed differently in the PVH according to their projection sites. Thirdly, we expressed tetanus toxin selectively in each CRH neuron to find physiological functions. This strategy is effective in classifying CRH neurons, tracking each neural pathway, and finding their role in feeding behavior.

Free Research Field

環境生理学

Academic Significance and Societal Importance of the Research Achievements

視床下部は、摂食調節に中心的な働きをしている。本研究で得られた結果は、視床下部の摂食抑制ニューロンの機能を調べると同時に、その投射先ニューロンをも明らかにできるという点で、今後、神経回路の研究の非常に有力な手段となりうる。肥満は様々な健康障害の原因となるため、効果的な摂食抑制薬の登場が望まれるが、現状では、副作用等の問題で有効に使用できる薬はほとんど皆無である。本研究で示すように、摂食抑制に関与するニューロンのタイプとその神経回路を明らかにすることは、特異的で副作用のない薬の開発に際してきわめて有効な情報を提供できると考える。