Ascorbate deficiency decreases dopamine release in gulo^-/- and APP/PSEN1 mice

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Dopamine (DA) is crucial for motivation, learning, and memory, but is prone to oxidation.
• Alzheimer's disease (AD) patients often show reduced motivation and sleep disturbances, indicating dopaminergic system deficits.
• Vitamin C (ascorbate, ASC) is a key brain antioxidant depleted in AD due to oxidative stress and poor diet.

Purpose of the Study:

• To investigate how vitamin C deficiency and AD pathology affect the dopamine system.
• To examine the impact on dopamine release, clearance, and levels in the brain.

Main Methods:

• Used gulo-/- mice (lacking vitamin C synthesis) crossed with APP/PSEN1 AD model mice.
• Administered sufficient or depleted vitamin C from weaning to 12 months.
• Analyzed dopamine neurotransmission using ex vivo fast-scan cyclic voltammetry and measured dopamine metabolites.

Main Results:

• Both vitamin C depletion and APP/PSEN1 genotype independently reduced dopamine release in the nucleus accumbens.
• Low vitamin C led to decreased dopamine and its metabolites (DOPAC, 3-MT, HVA) in striatal tissue.
• Combined vitamin C depletion and AD genotype reduced enzyme activity (pTH/TH ratio), indicating cumulative effects.

Conclusions:

• Vitamin C deficiency exacerbates age- and AD-related dopaminergic deficits.
• Reduced dopamine availability due to low vitamin C may contribute to non-cognitive AD symptoms like anhedonia and sleep disorders.