IMD signaling in the gut and the brain modulates Amyloid-beta-induced deficits in Drosophila

Tsung Chi Hsieh, Hsueh Cheng Chiang

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Aims: Evidence indicates accumulating Aβ peptides in brain activates immune responses in neuronal and peripheral system, which may collaboratively influence pathogenesis of Alzheimer's disease (AD). We aim to investigate whether regulating intestinal innate immune signaling ameliorates Aβ-induced impairments in Drosophila melanogaster. Main methods: Quantitative polymerase chain reaction (qPCR) was used to observe expression changes of innate immune responses related genes in brain and in gut under the circumstance of Aβ overexpressing in nerve system. Aversive olfactory conditioning and survival assay were used to investigate effects of modulating Attacin-A (AttA) and Dpitercin-A (DptA). Fluorometric assays of respiratory burst activity was introduced to explore whether reducing oxidative stress enables overexpressing intestinal AttA and DptA to reverse Aβ-induced deficits. Key findings: In vivo genetic analysis revealed that accumulating Aβ42 in neurons modulates innate immune signaling of the IMD pathway both in the brain and in the gut. Increased expression levels of the intestinal AttA and DptA improved learning performance and extended the lifespan of Aβ42 flies. The administration of apramycin led to alleviations of Aβ-induced behavioral changes, indicating that gram-negative bacteria are associated with the development of Aβ-induced pathologies. Further analysis showed that the neural expression of Aβ42 increased oxidative stress in the gut, which disrupted intestinal integrity and decreased learning performance. In addition, increased levels of AMPs targeting gram-negative bacteria and antioxidants reduced oxidative stress in the gut and reversed Aβ-induced behavioral damage. Significance: These findings suggest that innate immune responses in the gut play a pivotal role in modulating Aβ-induced pathologies.

原文English
文章編號122118
期刊Life Sciences
332
DOIs
出版狀態Published - 2023 11月 1

All Science Journal Classification (ASJC) codes

  • 一般生物化學,遺傳學和分子生物學
  • 藥理學、毒理學和藥劑學 (全部)

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