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Arch Biochem Biophys. 2019 Mar 15;663:120-128. doi: 10.1016/j.abb.2019.01.003. Epub 2019 Jan 8.

Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory.

Author information

1
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Japan; Geriatrics and Vascular Medicine, Tokyo Medical and Dental University, Japan.
2
Aging Neuroscience Research Team, Tokyo Metropolitan Institute of Gerontology, Japan.
3
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Japan.
4
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
5
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Japan.
6
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Japan. Electronic address: ishigami@tmig.or.jp.

Abstract

BACKGROUND:

Vitamin C (l-ascorbic acid, VC) and vitamin E (α-tocopherol, VE) play important physiological roles as endogenous antioxidants in many tissues and organs. However, their roles in the brain remain entirely elusive. We established senescence marker protein 30 (SMP30)/α-tocopherol transfer protein (αTTP) double knockout (DKO) mice as a novel VC and VE double-deficiency model and examined the effect of VC and VE double-deficiency on brain functions.

METHODS:

DKO and wild-type (WT) mice were divided into the following two groups: mice in the CE (+) group were supplied with sufficient amounts of VC and VE and mice in the CE (-) group were deficient in both VC and VE. After 8 weeks of CE (+) or CE (-) treatments, a battery of behavioral experiments was conducted to analyze cognitive functions, including memory, through the Morris water maze and Pavlovian fear conditioning tasks.

RESULTS:

The plasma VC and VE levels in DKO-CE (-) mice and VE level in WT-CE (-) mice were almost completely depleted after 8 weeks of the deficient treatment. The behavioral study revealed that the general behaviors, including locomotor activity and anxiety level, were not influenced by the CE (-) treatment in DKO and WT mice. However, in the Pavlovian fear conditioning task, DKO-CE (-) mice showed impaired conditioned fear memory compared with that of DKO-CE (+) mice. Furthermore, increased mRNA expression was observed in inflammatory-related genes, such as IL-6, TNFα, F4/80, and Mcp-1, in the hippocampus of DKO-CE (-) mice.

CONCLUSIONS:

The findings of this study provide evidence that VC and VE deficiency led to impaired conditioned fear memory possibly caused by neuroinflammation in the brain.

KEYWORDS:

Behavioral experiments; Neuroinflammation; SMP30; Vitamin C; Vitamin E; αTTP

PMID:
30629958
DOI:
10.1016/j.abb.2019.01.003

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