Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid

Area of Science:

• Neuroscience
• Biochemistry
• Aging Research

Background:

• Oxidative stress contributes to cognitive decline in aging and neurodegenerative diseases like Alzheimer's and Parkinson's.
• Ascorbic acid (vitamin C) is a key antioxidant, and its deficiency may exacerbate oxidative stress.
• Gulono-gamma-lactone oxidase (Gulo) knockout mice cannot synthesize ascorbic acid, making them reliant on dietary intake.

Purpose of the Study:

• To investigate the impact of varying ascorbic acid levels on oxidative stress, cognitive function, and motor abilities in Gulo-/- mice.
• To determine if reduced ascorbic acid and increased oxidative stress impair cognition or motor skills.
• To elucidate the role of ascorbic acid in maintaining motor function.

Main Methods:

• Gulo-/- mice were supplemented with ascorbic acid to achieve either sufficient or low physiological levels.
• Brain and liver ascorbic acid concentrations were measured.
• F(4)-neuroprostanes, markers of oxidative stress, were quantified in brain tissues.
• Cognitive function and motor abilities (strength, agility) were assessed.

Main Results:

• Ascorbic acid levels were higher in Gulo-sufficient mice compared to Gulo-low mice.
• F(4)-neuroprostanes were elevated in Gulo-low mice and in the cortex of Gulo-sufficient mice.
• All Gulo-/- mice exhibited normal cognition, but Gulo-low mice showed more severe deficits in strength and agility.
• Motor deficits correlated with lower ascorbic acid levels and higher oxidative stress markers.

Conclusions:

• Low ascorbic acid levels and elevated oxidative stress alone are insufficient to impair memory in Gulo-/- mice.
• Reduced ascorbic acid and increased oxidative stress appear responsible for exacerbated motor deficits in Gulo-low mice.
• Ascorbic acid plays a crucial role in maintaining motor abilities, independent of cognitive function.