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Exp Neurol. 2016 Jan;275 Pt 1:126-32. doi: 10.1016/j.expneurol.2015.10.002. Epub 2015 Oct 22.

Thidoredxin-2 overexpression fails to rescue chronic high calorie diet induced hippocampal dysfunction.

Author information

1
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States.
2
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, United States; Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China.
3
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio TX 78245, United States.
4
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.

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.

KEYWORDS:

High calorie diet; Hippocampus; Lipid peroxidation; Mitochondria; Oxidative stress; Synaptic plasticity; Thioredoxin

PMID:
26476179
PMCID:
PMC4688172
DOI:
10.1016/j.expneurol.2015.10.002
[Indexed for MEDLINE]
Free PMC Article

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