Vitamin K and the Nervous System: An Overview of its Actions

Ferland, Guylaine

doi:10.3945/an.111.001784

Cited by 155 publications

(156 citation statements)

References 69 publications

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“…S4 A-C), did not cause neuronal degeneration in vivo in nontransgenic littermates with an intact BSCB (Fig. 3 D-F), and did not interfere with the vitamin K-dependent synthetic pathway (29) as shown by normal levels of sphingolipids or Gas6 in spinal cord (Fig. S4 G and H).…”

Section: Significancementioning

confidence: 85%

Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice

Winkler

Sengillo

Sagare

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

200

169

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Humans with ALS and transgenic rodents expressing ALS-associated superoxide dismutase (SOD1) mutations develop spontaneous blood-spinal cord barrier (BSCB) breakdown, causing microvascular spinal-cord lesions. The role of BSCB breakdown in ALS disease pathogenesis in humans and mice remains, however, unclear, although chronic blood-brain barrier opening has been shown to facilitate accumulation of toxic blood-derived products in the central nervous system, resulting in secondary neurodegenerative changes. By repairing the BSCB and/or removing the BSCB-derived injurious stimuli, we now identify that accumulation of bloodderived neurotoxic hemoglobin and iron in the spinal cord leads to early motor-neuron degeneration in SOD1 G93A mice at least in part through iron-dependent oxidant stress. Using spontaneous or warfarin-accelerated microvascular lesions, motor-neuron dysfunction and injury were found to be proportional to the degree of BSCB disruption at early disease stages in SOD1 G93A mice. Early treatment with an activated protein C analog restored BSCB integrity that developed from spontaneous or warfarin-accelerated microvascular lesions in SOD1 G93A mice and eliminated neurotoxic hemoglobin and iron deposits. Restoration of BSCB integrity delayed onset of motor-neuron impairment and degeneration. Early chelation of blood-derived iron and antioxidant treatment mitigated early motor-neuronal injury. Our data suggest that BSCB breakdown contributes to early motor-neuron degeneration in ALS mice and that restoring BSCB integrity during an early disease phase retards the disease process.amyotrophic lateral sclerosis | neurodegeneration T he blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) prevent entry of toxic circulating molecules and cells into the central nervous system (CNS) (1). Amyotrophic lateral sclerosis (ALS) is the most prominent adult motor-neuron disorder resulting in progressive motor-neuron loss in the spinal cord, brainstem, and motor cortex (2). Most ALS cases are sporadic (90%) whereas 10% are familial ALS. Over twenty independent studies in postmortem human tissue and cerebrospinal fluid (CSF) sampling from living ALS patients have established that the BBB and BSCB are damaged in familial and sporadic ALS, as reviewed elsewhere (1, 3). This BBB and BSCB disruption has been shown by spinal-cord and/or motor-cortex accumulation of different plasma proteins (e.g., IgG, fibrin, thrombin), erythrocytes, erythrocyte-derived hemoglobin and iron-containing hemosiderin, elevated CSF/serum albumin ratios, and diminished expression or degradation of the BSCB tight-junction proteins (1, 3-5). Deposition of hemoglobin-derived iron within the CNS has also been shown in ALS patients (3, 6, 7). Because human postmortem studies reflect, however, end-stage disease, it has remained unclear as to which stage of disease is enhanced by BSCB disruption. Longitudinal CSF or BSCB imaging studies have yet to be performed in living ALS patients (3) to clarify whether spinal-cord vascular dysfunction contr...

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Section: Significancementioning

confidence: 85%

Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice

Winkler

Sengillo

Sagare

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

200

169

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“…Dietary K2 is processed in the liver and released into the circulation via high and low density lipoproteins that make them readily available for uptake into extrahepatic tissues [36][37][38]. Fermented foods such as cheese have significantly higher levels of K2 than milk.…”

Section: A Summary Of the Features Of Vitamin K2mentioning

confidence: 99%

Vitamin K2 and its Impact on Tooth Epigenetics

Gordeladze¹,

Landin²,

Johnsen³

et al. 2017

Vitamin K2 - Vital for Health and Wellbeing

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The impact of nutritional signals plays an important role in systemic-based «models» of dental caries. Present hypotheses now focus both on the oral environment and other organs, like the nervous system and brain. The tooth is subjected to shear forces, nourishing and cleansing, and its present "support system" (the hypothalamus/parotid axis) relays endocrine signaling to the parotid gland. Sugar consumption enhances hypothalamic oxidative stress (ROS), reversing dentinal fluid flow, thus creating an enhanced vulnerability to the oral bacterial flora. The acid, produced by the oral bacterial flora, then leads to erosion of the dentine, and an irreversible loss of dental enamel layers. This attack brings about inflammatory responses, yielding metalloproteinase-based "dissolution". However, vitamin K2 (i.e. MK-4/MK-7) may come to the rescue with its antioxidant property, locally (mouth cavity) or systemically (via the brain), thus sustaining/preserving hormone-induced dentinal fluid flow (encompassing oxidative stress) and boosting/magnifying bodily inflammatory responses. However, sugars may also reduce the tooth's natural defences through endocrine signaling, thus enhancing acid-supported enamel dentine erosion. Vitamin K2 sustains and improves the salivary buffering capacity via its impact on the secretion/flow of calcium and inorganic phosphates. Interestingly, primitive cultures' diets (low-sugar and high-K2 diets) preserve dental health.

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“…The risk of dementia associated with the low levels of vitamin B12 and folic acid, it has been greater also in subjects with good cognitive basic functions. There is a convincing evidence that vitamin K has important actions in the nervous system as a unique cofactor to the y-glutamyl carboxylase enzyme; vitamin K contributes to the biological activation of proteins Gas6 and protein S, ligands for the receptor tyrosine kinases of the TAM family (Tyr03, Axl, and Mer) (33). It has been suggested that vitamin K may have an effect on neuronal damage and that supplementation can lead benefit for the treatment of this disease.…”

Section: Vitamins: Focus On B12 B9 C K Dmentioning

confidence: 99%

Alzheimer's Disease: From Genes to Nutrition

et al. 2014

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Alzheimer's disease (AD) is widely identified as the most common cause of sporadic dementia. Its aetiology is still debated, as despite several hypotheses, different factors seem to play a role in its establishment and development. Recent studies have proposed a possible preventing role of nutrition. The weight loss typical of earlier phase of disease and the finding of malnutrition as a common trait between patients leads to hypothesize that a supplementation of specific nutrients seems to be useful and effective in terms of improvement of cognitive functions. Malnourished patients show also altered parameters when investigating inflammation markers: for example, hyperhomocysteinemia is a typical finding in elderly affected by dementia, and it can be prevented and corrected by using a proper nutrients supplementation. Pro-inflammatory state can be reduced with supplementation of polyunsaturated fatty acids, vitamins of the group Band phosphatidylserine, that can act reducing IL-lP (pro-inflammatory cytokine) and improving IL-IO (anti-inflammatory cytokine) synthesis. While investigating the role of nutrition, it seems to be deeply linked with genetic; a genetic onset AD-related could be latent and can be influenced by nutritional attitude. AD can be considered a sort of latent clinical condition that would disclose or not, depending also on micro-environment and nutritional parameters. The genetic expression can be influenced by assumptions or not of specific nutrients, with the promotion of different pro-or anti-inflammatory settings. The specific role of each micronutrient (in particular vitamins) and trace elements still needs to be punctuated, as they are involved in a pool of different reactions. Also genes acts not independently but in an interconnected pattern, in which the role of a single gene needs to be cleared, depending on others. This complex system of predisposing conditions and a possible role of nutrition as modulator of the inflammatory state is the object of this review.This review of the recent literature emphasizes how this field of study inherent nutrition is extremely promising in terms of prevention and of treatment of Alzheimer's disease. Moreover, the literature reinforces the need for early intervention in AD and suggests that multi nutritional intervention, targeting multiple aspects of the neurodegenerative process during the earliest possible phase in the development

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Vitamin K and the Nervous System: An Overview of its Actions

Cited by 155 publications

References 69 publications

Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice

Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice

Vitamin K2 and its Impact on Tooth Epigenetics

Alzheimer's Disease: From Genes to Nutrition

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