Study on mechanism of memory modification by infection with brain parasite, Toxoplasma

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19538
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: Nishikawa Yoshifumi 帯広畜産大学, 原虫病研究センター, 教授 (90431395)
• Research Collaborator: UMEDA Kousuke ; IHARA Fumiaki
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 感染症 / 中枢神経系 / 免疫 / トキソプラズマ / トランスクリプトーム

Outline of Final Research Achievements

Toxoplasma gondii infection is a risk factor for developing mental diseases and nervous diseases. Our previous study using experimental mouse showed that Toxoplasma infection impaired memory. Therefore, this study focused on Arc, which an important gene for memory formation, and aimed at elucidation of mechanism of Toxoplasma-dependent memory manipulation. We identified the parasite genes involved in upregulation of Arc expression and confirmed the activation of NFκB signaling by these genes. Analyses of mouse behavior focusing on Toll-like receptor 2, which is important for NFκB signaling, indicated that TLR2 deficiency increased the contextual and cued fear-conditioning behavior. Our results indicated the presence of parasite molecule for manipulation of host brain function.

Free Research Field

感染免疫学

Academic Significance and Societal Importance of the Research Achievements

近年の研究から、様々な精神疾患の発症や脳機能の異常には遺伝要因と環境要因の相互作用が重要であることが示唆されてきた。しかし環境要因が作用する機序は研究が進んでおらず、特にその中でも感染症が精神疾患や脳機能に与える影響については研究例が少ない。本研究によりトキソプラズマ感染による脳機能の障害が明らかとなり、Arc、NFκB、TLR2といった分子の関与が示唆された。すなわち、脳内の慢性炎症の状態が脳機能に負の影響を及ぼしており、治療・予防に向けた今後の応用研究の展開が可能になると考える。