Vitamin C deficiency increases basal exploratory activity but decreases scopolamine-induced activity in APP/PSEN1 transgenic mice.
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.
Harrison
F E
FE
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. Fiona.Harrison@Vanderbilt.edu
May
J M
JM
McDonald
M P
MP
D000682:Amyloid / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001206:Ascorbic Acid Deficiency / Q000235:genetics* / Q000401:mortality / Q000523:psychology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D050544:L-Gulonolactone Oxidase / Q000235:genetics; D015227:Lipid Peroxidation; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics*; D015996:Survival Rate
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid