Downregulation of Aquaporin 9 Exacerbates Beta-amyloid-induced Neurotoxicity in Alzheimer's Disease Models In vitro and In vivo

Neuroscience. 2018 Dec 1;394:72-82. doi: 10.1016/j.neuroscience.2018.09.016. Epub 2018 Sep 26.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, characterized by progressive cognitive dysfunction. Aquaporin 9 (AQP9) is an aquaglyceroporin membrane channel shown biophysically to conduct water, glycerol, and other small solutes. In our study, we reported for the first time an age-associated decrease in AQP9 mRNA and protein expressions in both hippocampus and cerebral cortex of APPswe/PS1dE9 (Tg) AD mice at 3, 6 and 10 months of age. Consistently, we observed a dose-dependent downregulation of AQP9 expression in PC12 cells after treatment with amyloid-beta protein 1-40 (Aβ1-40). Pre-treatment with AQP9 small interfering RNA led to a more severe neurotoxicity in PC12 cells in response to Aβ1-40. Furthermore, we corroborated that the active participation of AQP9 in AD progression is associated with Aβ-induced apoptosis both in vitro and in vivo. Taken together, our results reveal an important role of AQP9 in Aβ-induced pathogenesis of AD which deserves further investigation.

Keywords: APPswe/PS1dE9; Alzheimer's disease; apoptosis; aquaporin 9; beta-amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / toxicity*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Aquaporins / metabolism*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Survival
  • Cerebral Cortex / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Mice, Transgenic
  • PC12 Cells
  • Peptide Fragments / toxicity*
  • RNA, Messenger / metabolism
  • Rats

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Apoptosis Regulatory Proteins
  • Aqp9 protein, mouse
  • Aquaporins
  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein (1-40)