Anisomycin alleviates cognitive impairments and pathological features in 3xTg-AD mice

Neuropharmacology. 2024 Dec 15:261:110159. doi: 10.1016/j.neuropharm.2024.110159. Epub 2024 Sep 18.

Abstract

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the Western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aβ and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated.

Keywords: 3xTg-AD mice; Alzheimer's disease; Anisomycin; Learning and memory; Long-term potentiation; Neuroinflammation.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Anisomycin* / pharmacology
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / pathology
  • Disease Models, Animal
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Maze Learning / drug effects
  • Mice
  • Mice, Transgenic*
  • Microglia / drug effects
  • Microglia / metabolism
  • Neuroprotective Agents* / pharmacology
  • Spatial Memory / drug effects
  • tau Proteins / metabolism

Substances

  • Anisomycin
  • Neuroprotective Agents
  • tau Proteins
  • Amyloid beta-Peptides