Establishment and analysis of a mouse model of maternal neglect based on the dysfunction of synaptic adhesion molecule

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22777
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Kyoto Pharmaceutical University (2020); Wakayama Medical University (2019)
• Principal Investigator: Sekine Yuichi 京都薬科大学, 薬学部, 講師 (20396295)
• Co-Investigator(Kenkyū-buntansha): 久岡 朋子 和歌山県立医科大学, 医学部, 助教 (00398463)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 育児放棄 / シナプス接着分子 / 養育行動

Outline of Final Research Achievements

To investigate the molecular mechanisms of maternal neglect, we tried to establish a mouse model of maternal neglect and analyzed the maternal behaviors in Lrrn4 knockout (KO) mice. Lrrn4 KO mice had a normal sensory function, however, showed reduction of pup retrieval behavior and enhancement of exploration behavior in a novel environment. These results indicate that Lrrn4 KO mouse is a novel mouse model of maternal neglect, which exhibits normal recognition but reduced interest in pups. Histological analyses of brain and in vitro experiments of Lrrn4-binding proteins in neurons revealed that Lrrn4 signal transduction in the hippocampus may be involved in the normal maternal behaviors.

Free Research Field

社会医学、神経組織学、行動生理学

Academic Significance and Societal Importance of the Research Achievements

シナプス接着分子であるLrrn4は海馬神経回路に高発現し、その遺伝子欠損が母マウスの仔に対する注意力を低下させ、養育行動低下を惹起している可能性が示唆された。今後、本研究をさらに発展させ、海馬神経回路におけるLrrn4のシグナル伝達異常が養育行動異常を惹き起こす分子メカニズムを解明していく。本研究により、ヒトでなぜ不適切な養育行動をするのかという親側の要因に関して最も重要と考えられる「意識を仔に向けるか否かの選択」の神経基盤に、シナプス接着分子の異常が関連していることが明らかとなり、神経基盤に基づいたヒトの育児放棄の予防や治療法の開発へつながる可能性が期待できる。