Spatial Memory Dysfunction Induced by Vitamin C Deficiency Is Associated with Changes in Monoaminergic Neurotransmitters and Aberrant Synapse Formation.

Stine Hansen,Anne Schou-Pedersen,Pernille Tveden-Nyborg,Jens Lykkesfeldt

doi:10.3390/antiox7070082

Abstract

Vitamin C (vitC) is important in the developing brain, acting both as an essential antioxidant and as co-factor in the synthesis and metabolism of monoaminergic neurotransmitters. In guinea pigs, vitC deficiency results in increased oxidative stress, reduced hippocampal volume and neuronal numbers, and deficits in spatial memory. This study investigated the effects of 8 weeks of either sufficient (923 mg vitC/kg feed) or deficient (100 mg vitC/kg feed) levels of dietary vitC on hippocampal monoaminergic neurotransmitters and markers of synapse formation in young guinea pigs with spatial memory deficits. Western blotting and high performance liquid chromatography (HPLC) were used to quantify the selected markers. VitC deficiency resulted in significantly reduced protein levels of synaptophysin (p = 0.016) and a decrease in 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio (p = 0.0093). Protein expression of the N-methyl-d-aspartate receptor subunit 1 and monoamine oxidase A were reduced, albeit not reaching statistical significance (p = 0.0898 and p = 0.067, respectively). Our findings suggest that vitC deficiency induced spatial memory deficits might be mediated by impairments in neurotransmission and synaptic development.

Highlights

Vitamin C deficiency is a surprisingly common nutritional insufficiency affecting around15% of the Western population [1,2,3], including subpopulations such as pregnant women and young children [4,5]
We have previously shown impaired hippocampal function measured by decreased spatial memory performance in the Morris Water Maze, in coherence with significantly reduced hippocampal neuron numbers in guinea pigs subjected to Vitamin C (vitC) deficiency during early life and until reproductive maturity [10]
The dietary regimes resulted in ascorbate (Asc; the reduced and active form of vitC) plasma concentrations of 104 ± 34.2 μM in CTRL and 8.5 ± 3.7 μM in DEF, and brain Asc levels of 1256 ± 87.4 nmol/g tissue and 519 ± 99.6 nmol/gram tissue in CTRL and DEF, respectively

Summary

Introduction

Vitamin C (vitC) deficiency is a surprisingly common nutritional insufficiency affecting around15% of the Western population [1,2,3], including subpopulations such as pregnant women and young children [4,5]. The vitamin is a powerful antioxidant, and crucial in the developing brain, where antioxidant defenses are still immature and a high cellular metabolism gives rise to increased levels of reactive oxygen species [6,7]. In the face of dietary depletion, vitC levels in the brain are maintained at approximately 25% of saturated values—as opposed to more extensive reductions in most other organs [8,9], suggesting that the nutrient is of high importance in this tissue. Life vitC deficiency has been shown to cause impairments in spatial memory, decrease hippocampal volume and neuron numbers in guinea pigs [10,11], a species dependent on dietary vitC akin to humans [12,13].

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