Sodium butyrate reduces brain amyloid-β levels and improves cognitive memory performance in an Alzheimer's disease transgenic mouse model at an early disease stage

W. M. A. D. Binosha Fernando, Ian J. Martins, Michael Morici, Prashant Bharadwaj, Stephanie R. Rainey-Smith, Wei Ling Florence Lim, Ralph N. Martins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and neuropathological features, including abnormal deposition of amyloid-β (Aβ) peptides, intracellular neurofibrillary tangles, and neuronal death. Identifying therapeutics which can reduce memory deficits at an early stage of the disease has the advantage of slowing or even reversing disease progression before irreversible brain damage has occurred. Consequently, in this study, we investigated the ability of the histone deacetylase inhibitor sodium butyrate (NaB) to attenuate memory deficits in the 5xFAD mouse model of AD following a 12-week feeding regimen. 5xFAD mice demonstrate a unique time course of Aβ pathology, developing Aβ plaques as early as 2 months. Male mice were assigned to either a control diet or a NaB-supplemented diet which was administered at either 5 mg/kg/day, or 15 mg/kg/day for 12 weeks (each group, N = 15). Supplementation commenced at an early disease stage (8-10 weeks of age). Behavioral testing (contextual and cued fear conditioning) was undertaken, and brain Aβ levels measured, at the end of the 12-week intervention. NaB had profound effects on Aβ levels and on associative learning and cognitive functioning. A 40% reduction in brain Aβ levels and a 25% increase in fear response in both the cued and contextual testing was observed in the NaB-treated animals compared to the control group. These findings suggest that NaB warrants further investigation as a potential therapeutic agent in the treatment of cognitive deficits associated with early stages of AD.

Original languageEnglish
Pages (from-to)91-99
Number of pages9
JournalJournal of Alzheimer's Disease
Volume74
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Alzheimer's disease
  • amyloid-β
  • fear conditioning
  • sodium butyrate

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