1. Effect of high-fat diet on cognitive impairment in triple-transgenic mice model of Alzheimer's disease
- Author
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Chan Lee, Gyu Hwan Park, Jung-Hee Jang, and Saroj Kumar Sah
- Subjects
Male ,0301 basic medicine ,Genetically modified mouse ,medicine.medical_specialty ,Normal diet ,NF-E2-Related Factor 2 ,Transgene ,Tau protein ,Biophysics ,Morris water navigation task ,Mice, Transgenic ,tau Proteins ,Diet, High-Fat ,medicine.disease_cause ,Biochemistry ,Lipid peroxidation ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Cognition ,Sex Factors ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Protein kinase B ,Amyloid beta-Peptides ,biology ,Brain ,Cell Biology ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,chemistry ,Immunology ,biology.protein ,Female ,Cognition Disorders ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress - 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.
- Published
- 2017
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