title: Thidoredxin-2 overexpression fails to rescue chronic high calorie diet induced hippocampal dysfunction.
abstract: A high calorie diet (HCD) can impair hippocampal synaptic plasticity and cognitive function in animal models. Mitochondrial thioredoxin 2 (TRX-2) is critical for maintaining intracellular redox status, but whether it can protect against HCD-induced impairment of synaptic plasticity is unknown. We found that levels of TRX-2 are reduced in the hippocampus of wild type mice maintained for 8 months on a HCD, and that the mice on the HCD exhibit impaired hippocampal synaptic plasticity (long-term potentiation at CA1 synapses) and cognitive function (novel object recognition). Transgenic mice overexpressing human TRX-2 (hTRX-2) exhibit increased resistance to diquat-induced oxidative stress in peripheral tissues. However, neither the HCD nor hTRX-2 overexpression affected levels of lipid peroxidation products (F2 isoprostanes) in the hippocampus, and hTRX-2 transgenic mice were not protected against the adverse effects of the HCD on hippocampal synaptic plasticity and cognitive function. Our findings indicate that TRX-2 overexpression does not mitigate adverse effects of a HCD on synaptic plasticity, and also suggest that oxidative stress may not be a pivotal factor in the impairment of synaptic plasticity and cognitive function caused by HCDs.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States; Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
authors.forename: Roy G
authors.initials: RG
authors.lastname: Cutler
authors.affiliation: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio TX 78245, United States.
authors.forename: Randy
authors.initials: R
authors.lastname: Strong
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. Electronic address: mark.mattson@nih.gov.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D004032:Diet; D028441:F2-Isoprostanes / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D028441:F2-Isoprostanes; D013879:Thioredoxins
keywords: High calorie diet; Hippocampus; Lipid peroxidation; Mitochondria; Oxidative stress; Synaptic plasticity; Thioredoxin