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

Hansen, Stine Normann; Schou-Pedersen, Anne Marie V.; Lykkesfeldt, Jens; Tveden‐Nyborg, Pernille

doi:10.3390/antiox7070082

Cited by 8 publications

(5 citation statements)

References 48 publications

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“…Several preclinical studies have illustrated the importance of vitC in early development, in particular that of the brain and cognition [60,63,98,99,100]. In humans, studies have shown that poor maternal vitC status results in increased fetal oxidative stress, impaired implantation and increased risk of complications including preeclampsia [101,102].…”

Section: Factors Affecting Vitamin C Homeostasis and Requirementsmentioning

confidence: 99%

The Pharmacokinetics of Vitamin C

2019

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The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized distribution pattern with a diverse range of organ concentrations of vitC at homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. The homeostasis of vitC is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors such as smoking and diet, as well as diseases. Going from physiological to pharmacological doses, vitC pharmacokinetics change from zero to first order, rendering the precise calculation of dosing regimens in, for example, cancer and sepsis treatment possible. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of intervention studies, giving rise to misinterpretations and erroneous conclusions. The present review outlines the diverse aspects of vitC pharmacokinetics and examines how they affect vitC homeostasis under a variety of conditions.

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Section: Factors Affecting Vitamin C Homeostasis and Requirementsmentioning

confidence: 99%

The Pharmacokinetics of Vitamin C

2019

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“…There was no apparent effect on SOD, GSH or MDA levels in the brain, suggesting that the effects of deficiency could be due to mechanisms not directly associated with oxidative stress [185]. In agreement with an effect on more specific functions, reduced levels of synaptophysin and alterations in serotonin metabolites in the hippocampus of deficient animals suggested impaired neuronal signal transmission, potentially exacerbating the consequences of the lower neuronal numbers [266].…”

Section: Changes In Brain Structure and Functionmentioning

confidence: 74%

“…Reduced spatial memory competence. [185,266] BDNF: brain-derived neurotrophic factor; deficiency: low vitC supplementation; depletion: no vitC supplementation; GSH: glutathione; MDA: malondialdehyde; PD: postnatal day; SOD: superoxide dismutase; wks: weeks.…”

Section: Changes In Brain Structure and Functionmentioning

confidence: 99%

Vitamin C Deficiency in the Young Brain—Findings from Experimental Animal Models

Tveden‐Nyborg

2021

Nutrients

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Severe and long-term vitamin C deficiency can lead to fatal scurvy, which is fortunately considered rare today. However, a moderate state of vitamin C (vitC) deficiency (hypovitaminosis C)—defined as a plasma concentration below 23 μM—is estimated to affect up to 10% of the population in the Western world, albeit clinical hallmarks in addition to scurvy have not been linked to vitC deficiency. The brain maintains a high vitC content and uniquely high levels during deficiency, supporting vitC’s importance in the brain. Actions include both antioxidant and co-factor functions, rendering vitamin C deficiency likely to affect several targets in the brain, and it could be particularly significant during development where a high cellular metabolism and an immature antioxidant system might increase sensitivity. However, investigations of a non-scorbutic state of vitC deficiency and effects on the developing young brain are scarce. This narrative review provides a comprehensive overview of the complex mechanisms that regulate vitC homeostasis in vivo and in the brain in particular. Functions of vitC in the brain and the potential consequences of deficiency during brain development are highlighted, based primarily on findings from experimental animal models. Perspectives for future investigations of vitC are outlined.

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“…Antioxidants contribute to the protection of nerve cells from damage and improve neurotransmitter function, which can help prevent and treat depression. Specifically, the antioxidant vitamin C has been found to promote the release of neurotransmitters such as dopamine, norepinephrine, and 5-hydroxytryptamine from neurons, increasing the levels of neurotransmitters that influence communication between neurons 58 . The fifth is the gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

Association of composite dietary antioxidant index with depression and all-cause mortality in middle-aged and elderly population

Luo,

Xu,

Sun

et al. 2024

Sci Rep

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Current research has shown an increasing acceptance of interventions for depression through dietary modifications. However, whether composite dietary antioxidant index (CDAI) is associated with depression and all-cause mortality in middle-aged and elderly population remains unknown. This study aimed to explore those associations in American middle-aged and elderly population. Weighted logistic regression models and weighted Cox proportional hazard regression models were used to assess the association of CDAI, covariates, depression, and all-cause mortality, respectively. The stability of the results was also determined by a linear trend test based on CDAI quintiles. Restricted cubic spline curves were employed to test for non-linear relationships. In the model adjusted for all covariates, significant associations were found with the ORs (95% CI) for CDAI and depression [0.77 (0.67, 0.89)] and the HRs (95% CI) for CDAI with all-cause mortality[0.91 (0.83, 1.00)]. Upon conducting restricted cubic spline curves, we found that the association between CDAI and depression was linear, whereas the association between CDAI and all-cause mortality was non-linear with an inflection point of -0.19. Statistical significance was only found before the inflection point. In this study of middle-aged and elderly Americans, CDAI was linearly negatively associated with depression and non-linearly negatively associated with all-cause mortality.

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

Cited by 8 publications

References 48 publications

The Pharmacokinetics of Vitamin C

The Pharmacokinetics of Vitamin C

Vitamin C Deficiency in the Young Brain—Findings from Experimental Animal Models

Association of composite dietary antioxidant index with depression and all-cause mortality in middle-aged and elderly population

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