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

Pharmacology, Biochemistry, and Behavior
Fiona E HarrisonM P McDonald

Abstract

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.

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Citations

Dec 24, 2011·PloS One·Anandh Dhanushkodi, Michael P McDonald
Apr 26, 2014·Nutrients·Fiona E HarrisonMaria Cristina Polidori
Mar 25, 2014·Genes, Brain, and Behavior·T J FlaniganM P McDonald
Jul 23, 2015·Molecular Neurobiology·Ewa NiedzielskaMałgorzata Filip
Feb 28, 2017·Genes, Brain, and Behavior·Y AkkhawattanangkulM P McDonald
Oct 31, 2012·Journal of Neurochemistry·Margaret S WardFiona E Harrison
Aug 17, 2020·Journal of Neurochemistry·David C ConsoliFiona E Harrison

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