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Modulation of Alzheimer's disease brain pathology in mice by gut bacterial depletion: the role of IL-17a.
Hao, Wenlin; Luo, Qinghua; Tomic, Inge; Quan, Wenqiang; Hartmann, Tobias; Menger, Michael D; Fassbender, Klaus; Liu, Yang.
Afiliación
  • Hao W; Department of Neurology, Saarland University, Homburg/Saar, Germany.
  • Luo Q; German Institute for Dementia Prevention (DIDP), Saarland University, Homburg/Saar, Germany.
  • Tomic I; Department of Neurology, Saarland University, Homburg/Saar, Germany.
  • Quan W; German Institute for Dementia Prevention (DIDP), Saarland University, Homburg/Saar, Germany.
  • Hartmann T; Department of Neurology, The second affiliated hospital of Nanchang University, Nanchang, China.
  • Menger MD; Department of Neurology, Saarland University, Homburg/Saar, Germany.
  • Fassbender K; German Institute for Dementia Prevention (DIDP), Saarland University, Homburg/Saar, Germany.
  • Liu Y; Department of Neurology, Saarland University, Homburg/Saar, Germany.
Gut Microbes ; 16(1): 2363014, 2024.
Article en En | MEDLINE | ID: mdl-38904096
ABSTRACT
Gut bacteria regulate brain pathology of Alzheimer's disease (AD) patients and animal models; however, the underlying mechanism remains unclear. In this study, 3-month-old APP-transgenic female mice with and without knock-out of Il-17a gene were treated with antibiotics-supplemented or normal drinking water for 2 months. The antibiotic treatment eradicated almost all intestinal bacteria, which led to a reduction in Il-17a-expressing CD4-positive T lymphocytes in the spleen and gut, and to a decrease in bacterial DNA in brain tissue. Depletion of gut bacteria inhibited inflammatory activation in both brain tissue and microglia, lowered cerebral Aß levels, and promoted transcription of Arc gene in the brain of APP-transgenic mice, all of which effects were abolished by deficiency of Il-17a. As possible mechanisms regulating Aß pathology, depletion of gut bacteria inhibited ß-secretase activity and increased the expression of Abcb1 and Lrp1 in the brain or at the blood-brain barrier, which were also reversed by the absence of Il-17a. Interestingly, a crossbreeding experiment between APP-transgenic mice and Il-17a knockout mice further showed that deficiency of Il-17a had already increased Abcb1 and Lrp1 expression at the blood-brain barrier. Thus, depletion of gut bacteria attenuates inflammatory activation and amyloid pathology in APP-transgenic mice via Il-17a-involved signaling pathways. Our study contributes to a better understanding of the gut-brain axis in AD pathophysiology and highlights the therapeutic potential of Il-17a inhibition or specific depletion of gut bacteria that stimulate the development of Il-17a-expressing T cells.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encéfalo / Ratones Transgénicos / Interleucina-17 / Modelos Animales de Enfermedad / Enfermedad de Alzheimer / Microbioma Gastrointestinal Límite: Animals / Female / Humans Idioma: En Revista: Gut Microbes Año: 2024 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encéfalo / Ratones Transgénicos / Interleucina-17 / Modelos Animales de Enfermedad / Enfermedad de Alzheimer / Microbioma Gastrointestinal Límite: Animals / Female / Humans Idioma: En Revista: Gut Microbes Año: 2024 Tipo del documento: Article País de afiliación: Alemania