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

Yong Liu, Ying Yang, Hui Dong, Roy G. Cutler, Randy Strong, Mark P. Mattson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)126-132
Number of pages7
JournalExperimental Neurology
Volume275
DOIs
StatePublished - Jan 1 2016

Fingerprint

Neuronal Plasticity
Thioredoxins
Diet
Cognition
Transgenic Mice
Hippocampus
Oxidative Stress
Diquat
F2-Isoprostanes
Long-Term Potentiation
Synapses
Lipid Peroxidation
Oxidation-Reduction
Animal Models

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Thidoredxin-2 overexpression fails to rescue chronic high calorie diet induced hippocampal dysfunction. / Liu, Yong; Yang, Ying; Dong, Hui; Cutler, Roy G.; Strong, Randy; Mattson, Mark P.

In: Experimental Neurology, Vol. 275, 01.01.2016, p. 126-132.

Research output: Contribution to journalArticle

Liu, Yong ; Yang, Ying ; Dong, Hui ; Cutler, Roy G. ; Strong, Randy ; Mattson, Mark P. / Thidoredxin-2 overexpression fails to rescue chronic high calorie diet induced hippocampal dysfunction. In: Experimental Neurology. 2016 ; Vol. 275. pp. 126-132.
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