Exploring a novel mechanism of homeoprotein transfer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19374
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Niigata University
• Principal Investigator: SUGIYAMA Sayaka 新潟大学, 医歯学系, 准教授 (10360570)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 回路形成 / ホメオ蛋白質 / 遺伝子導入法 / ドーパミン作動性細胞

Outline of Final Research Achievements

Brain networks are intensively shaped by experience in early life. However, much about the mechanism of experience-dependent plasticity remains unclear. In this study, we focused on effect of homeoprotein transfer on development of fear processing. Conditioned fear is erased by extinction learning in young children but not in adulthood. In fear conditioning analysis, fear responses to visual cue were significantly decreased in homeoprotein depletion although fear responses to tone cue were similarly detected compared to control mice. Corresponding to a role of homeoprotein transfer in maturation of amygdala circuits, recall of tone-cued fear memory was declined in these mice. Thus, homeoprotein transfer may promote the network function in fear development and memory. It would be important to elucidate the direct role of experience-dependent transfer of homeoprotein in emotional development by using newly established single-cell electroporation technique.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、ホメオ蛋白質が恐怖の情動を担う回路を移動し、回路の発達を促すことを初めて明らかにした。ホメオ蛋白質の脳内移動の報告は未だ少なく、移動の新たな効能を示す成果となった。今後、恐怖の体験によりホメオ蛋白質の移動が促進されるのかを明らかにすることが重要である。ヒトのホメオ蛋白質の変異からは、発達・睡眠障害が報告されている。幼児期の睡眠障害は自閉症にも関与し、彼らを悩ませる危険感受性の弱さやフラッシュバックとの関連が疑われる。本成果は、睡眠障害に関与するホメオ蛋白質が、恐怖情動の発達を促すことを示唆しており、睡眠障害と恐怖情動のバランスを同時に整える新たな治療法につながると期待される。