Analysis of microbiota as a missing link between excercise and adult hippocampal neurogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22812
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Jinno Shozo 九州大学, 医学研究院, 教授 (10325524)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 腸内細菌叢 / 認知機能 / 成体海馬神経新生 / 短鎖脂肪酸 / 運動 / 加齢 / ミクログリア

Outline of Final Research Achievements

We aimed to understand the potential role of microbiota and voluntary exercise in brain function. To this end, we analyzed young adult mice that exhibited higher locomotor activity and middle-aged mice that showed reduced locomotor activity. Interestingly, alterations in microbiota by probiotics (Lactobacillus casei) promoted the adult hippocampal neurogenesis and improved memory performance in middle-aged mice. By contrast, the administration of microbiota did not affect the results in young adult mice. The concentrations of short-chain fatty acid in feces were increased by probiotics, and administration of short-chain fatty acid promoted adult hippocampal neurogenesis in middle-aged mice. Pharmacological depletion of microglia by PLX3397 inhibited the effects of probiotics on memory performance and adult hippocampal neurogenesis. These findings suggest that microbiota may affect brain function via modulation of microglial activity in middle aged mice.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

運動機能が低下する高齢者にみられるロコモティブシンドロームは、認知機能の低下や要介護に至るリスクを高めると考えられている。本研究で我々は、プロバイオティクスによる腸内細菌叢の改変は、運動量の多い若齢マウスの認知機能には影響を与えないが、運動量が減少している加齢マウスの認知機能を改善し、脳の免疫細胞であるミクログリアを介して成体海馬神経新生を促進することを発見した。本研究の意義は、加齢による筋力の低下や関節の痛みのため、適切な運動をすることが困難な高齢者にとり、腸内細菌叢の改善は認知機能低下を予防する可能性があることを明らかにした点にある。