Effect of high-fat diet on cognitive impairment in triple-transgenic mice model of Alzheimer's disease

Saroj Kumar Sah, Chan Lee, Jung Hee Jang, Gyu Hwan Park

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

High-fat diet (HFD)-induced obesity is a risk factor for cognitive impairment in Alzheimer's disease (AD). It has been reported that two typical neuropathological markers of AD, β-amyloid (Aβ) peptide and hyperphosphorylated protein tau can cause neuronal apoptosis via oxidative stress, which ultimately leads to cognitive dysfunction. In this study, we tried to explore the molecular pathway underlying memory impairment in young AD transgenic mice model in response to HFD. We maintained non-transgenic control mice (non-Tg) and triple transgenic AD (3xTg-AD) mice aged 8 weeks on either normal diet (ND) containing 10% fat or HFD (60% fat) for 16 weeks. Cognitive functions were evaluated by Morris water maze and Y-maze tests. Behavioral tests showed a significant memory impairment in 3xTg-AD mice fed with HFD. HFD did not alter the levels of Aβ and phospho-tau protein in the cortical region regardless of groups. However, 3xTg-AD mice fed with HFD exhibited increased neuronal oxidative stress and apoptosis as assessed by augmentation of lipid peroxidation, activation of caspase-3 and elevated ratio of Bax/Bcl-2. Furthermore, HFD markedly reduced the activation of redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2) by suppressing its up-stream regulatory protein kinase B/Akt as well as down-stream targets such as heme oxygenase-1 and manganese superoxide dismutase in these mice. Our findings suggest that HFD may accelerate cognitive impairment by enhancing oxidative stress and aggravating neuronal apoptosis via inactivation of Nrf2 signaling pathway.

Original languageEnglish
Pages (from-to)731-736
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number1
DOIs
StatePublished - 4 Nov 2017

Keywords

  • Alzheimer's disease
  • Apoptosis
  • Cognitive impairment
  • High-fat diet
  • Oxidative stress

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