Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice.

Harrison FE, May JM, McDonald MP
Pharmacol Biochem Behav. 2010 94 (4): 543-52

PMID: 19941887 · PMCID: PMC2828687 · DOI:10.1016/j.pbb.2009.11.009

Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease.

Copyright 2009 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Amyloid Amyloid beta-Protein Precursor Animals Ascorbic Acid Ascorbic Acid Deficiency Brain Exploratory Behavior Female L-Gulonolactone Oxidase Lipid Peroxidation Male Maze Learning Mice Mice, Transgenic Oxidative Stress Presenilin-1 Survival Rate

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