The investigation between depression and interleukin 18 targeting for new therapy.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16404
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Hyogo Medical University
• Principal Investigator: Yamanishi Kyosuke 兵庫医科大学, 医学部, 特任助教 (50626786)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: インターロイキン18 / IL-18 / depression / mitochondria / hippocampas / neurogenesis / learning and memory

Outline of Final Research Achievements

IL-18-deficient (Il18-/-) male mice were generated and Il18+/+ mice were used as controls. Compared with Il18+/+ mice, Il18-/- mice had impaired learning and memory and exhibited lower motivation. In the Il18-/- mice, degenerated mitochondria were detected in synaptic terminals in the molecular layer, the polymorphic layer, and in mossy fibers in the dentate gyrus, suggesting mitochondrial abnormalities. Because of the degeneration of mitochondria, in which pro-apoptotic molecules were upregulated and anti-apoptotic factors were decreased, apoptosis inducers were not cleaved, indicating inhibition of apoptosis. In addition, neurogenesis in the dentate gyrus and the maturity of neuronal cells were decreased in the Il18-/- mice, while intracerebral administration of recombinant IL-18 promoted significant recovery of neurogenesis. Our findings suggested that IL-18 was indispensable for mitochondrial homeostasis, normal neuronal maturation and hippocampal function.

Free Research Field

うつ病

Academic Significance and Societal Importance of the Research Achievements

炎症性サイトカインのインターロイキン18(IL-18)は、免疫機能に深く関与しているが、近年うつ病との関連も言われている。本研究よりIL-18が中枢神経細胞に深い関わりがあり、IL-18が欠損する事で海馬機能不全を呈し、記銘力障害、抑うつ様行動変化等の精神症状を呈し、IL-18を補うことで一部の改善を認めた事を報告した。抑うつやストレスが関わる精神疾患に対するIL-18の治療標的の可能性を探る目的で行い、治療満足度の低いうつ病に新たな治療法につながる可能性を示唆した。