scholarly journals Decreased content of ascorbic acid (vitamin C) in the brain of knockout mouse models of Na+,K+-ATPase-related neurologic disorders

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246678
Author(s):  
Keiko Ikeda ◽  
Adriana A. Tienda ◽  
Fiona E. Harrison ◽  
Kiyoshi Kawakami

Na+,K+-ATPase is a crucial protein responsible for maintaining the electrochemical gradients across the cell membrane. The Na+,K+-ATPase is comprised of catalytic α, β, and γ subunits. In adult brains, the α3 subunit, encoded by ATP1A3, is predominantly expressed in neurons, whereas the α2 subunit, encoded by ATP1A2, is expressed in glial cells. In foetal brains, the α2 is expressed in neurons as well. Mutations in α subunits cause a variety of neurologic disorders. Notably, the onset of symptoms in ATP1A2- and ATP1A3-related neurologic disorders is usually triggered by physiological or psychological stressors. To gain insight into the distinct roles of the α2 and α3 subunits in the developing foetal brain, whose developmental dysfunction may be a predisposing factor of neurologic disorders, we compared the phenotypes of mouse foetuses with double homozygous knockout of Atp1a2 and Atp1a3 (α2α3-dKO) to those with single knockout. The brain haemorrhage phenotype of α2α3-dKO was similar to that of homozygous knockout of the gene encoding ascorbic acid (ASC or vitamin C) transporter, SVCT2. The α2α3-dKO brain showed significantly decreased level of ASC compared with the wild-type (WT) and single knockout. We found that the ASC content in the basal ganglia and cerebellum was significantly lower in the adult Atp1a3 heterozygous knockout mouse (α3-HT) than in the WT. Interestingly, we observed a significant decrease in the ASC level in the basal ganglia and cerebellum of α3-HT in the peripartum period, during which mice are under physiological stress. These observations indicate that the α2 and α3 subunits independently contribute to the ASC level in the foetal brain and that the α3 subunit contributes to ASC transport in the adult basal ganglia and cerebellum. We propose that decreases in ASC levels may affect neural network development and are linked to the pathophysiology of ATP1A2- and ATP1A3-related neurologic disorders.

2015 ◽  
Vol 16 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Dragan M. Pavlović ◽  
Merdin Š. Markišić ◽  
Aleksandra M. Pavlović

Abstract Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain. Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer’s disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.


Scurvy ◽  
2018 ◽  
pp. 268-276
Author(s):  
James May ◽  
Fiona Harrison

This chapter discusses the neurological basis of scurvy. The physical symptoms of extreme vitamin C deficiency, i.e., scurvy, have been described in numerous ships' logs, diaries, and medical texts, stretching back for hundreds of years. Examples include hemorrhage, and the characteristic broken blood vessels under the skin; and hyperkeratosis, or changes in hair such as thinning, alopecia, and corkscrew hairs on the limbs. However, modern techniques in neuroscience research have revealed the highly complex roles of vitamin C in the brain, which may have changed the behavior of those experiencing long periods of nutritional deficiencies. The most important roles for vitamin C, also known as ascorbate and ascorbic acid, are in the synthesis of neurotransmitters, the chemical messengers of the brain, and for protection of neurons (brain cells) against damage by a constant barrage of free radicals.


2002 ◽  
Vol 8 (5) ◽  
pp. 514-517 ◽  
Author(s):  
Sotiria Sotiriou ◽  
Suzana Gispert ◽  
Jun Cheng ◽  
Yaohui Wang ◽  
Amy Chen ◽  
...  

1942 ◽  
Vol s2-83 (331) ◽  
pp. 259-298
Author(s):  
S. A. BARNETT ◽  
G. BOURNE

1. The distribution of ascorbic acid (vitamin C) in the cells and tissues of chick embryos, from the fourth day of incubation to 2 days after hatching, has been studied by the acid silver nitrate method. 2. Mesenchymatous cells show a reaction when undergoing histo-differentiation into cartilage, bone, muscle, dermis, vitreous humour, adrenal cortex, meninges. Differentiated cartilage cells do not contain ascorbic acid except in areas of proliferation; the cartilaginous matrix may contain it where the cartilage is about to be replaced by bone. Osteoblasts show no reaction at first, a slight reaction when they become surrounded by calcified tissue, and in some cases a strong reaction in older bone. Ascorbic acid is associated with the ‘osteogenic’ fibres immediately before calcification, and is also present in newly calcified trabeculae. 3. In blood ascorbic acid is present in erythrocytes and plasma; evidence is presented for the view that it accumulates in the older erythrocytes. Cells resembling histiocytes have been observed in muscle, containing high concentrations; no other leucocytes have been observed to show a reaction. 4. Liver shows a strong diffuse reaction in early embryos, but none at all after the tenth day. At the latter age ascorbic acid has been detected in a localized area of cytoplasm which appears to be the Golgi substance. 5. The thyroid shows no reaction at the tenth day, or after hatching, but has been seen to give a reaction at the twelfth day. 6. Various epithelia of the organs of special sense, and of the alimentary canal, contain ascorbic acid. 7. The adrenal, both cortex and medulla, first shows a reaction at the twelfth day; by the fourteenth day typical distributions appear, though the amount of ascorbic acid present continues to increase after that age. The reaction shown by the medullary cells is much stronger than that shown by the cortical elements, a reversal of the condition in the mammalian adrenal. 8. Ascorbic acid was not detected in the testis. In the ovary it appears at the fourteenth day, in a very restricted area of the cytoplasm of certain large cells in the cortex; at later ages the distribution is similar, but the impregnated area in each cell is larger. The cells concerned are believed to be the germ-cells. 9. The mesonephros contains ascorbic acid from the fifth to the sixteenth days in the tubule cells, the glomeruli, and the lumina of the tubules. In the tubule epithelia the deposit may be localized at one pole of the cell. The metanephros begins to show a reaction at the twelfth day; here, too, the tubule cells frequently have a deposit at one pole. 10. In the cells of the central nervous system ascorbic acid may be localized in a small area near the nucleus (probably the Golgi material), round the whole of the nuclear surface, or in the axon and axon hillock; or it may be diffusely distributed through the cytoplasm. A reaction is shown at the fourth day, especially in the axons of certain cells of the brain and spinal cord; later, localization in the Golgi substance becomes very general in most parts of the brain and cord. A reaction is also shown in ganglion cells, the meninges, and the choroid plexuses. The specific distributions in the principle parts of the central nervous system are described. 11. Results are discussed in the sections on each organ or tissue. In the general discussion it is pointed out that the observations described are concordant with the view that ascorbic acid is frequently localized in the Golgi material. On the other hand, the evidence is that there is no specific relation with the ‘chondriome’ in the embryonic cells of the fowl. The role of ascorbic acid in development is also briefly discussed.


1979 ◽  
Vol 44 (11) ◽  
pp. 3395-3404 ◽  
Author(s):  
Pavel Posádka ◽  
Lumír Macholán

An oxygen electrode of the Clark type, coated by a thin, active layer of chemically insolubilized ascorbate oxidase from squash peelings specifically detects by measuring oxygen uptake 10 to 400 μg of ascorbic acid in 3 ml of phosphate buffer. The record of current response to substrate addition lasts 1-2 min. The ascorbic acid values determined in various samples of fruit juices are in good agreement with the data obtained by titration and polarography. The suitable composition of the membrane and its lifetime and stability during long-term storage are described; optimal reaction conditions of vitamin C determination and the possibilities of interference of other compounds are also examined. Of the 35 phenols, aromatic amines and acids tested chlorogenic acid only can cause a positive error provided that the enzyme membrane has been prepared from ascorbate oxidase of high purity.


Author(s):  
Mensura Altumbabic ◽  
Marc R. Del Bigio ◽  
Scott Sutherland

ABSTRACT:Background:Transtentorial herniation of large cerebral fragments is a rare phenomenon.Method:Case StudyResults:Examination of the brain of a 35-year-old male showed massive intracerebral hemorrhage resulting in displacement of basal ganglia components into the fourth ventricle.Conclusions:Sufficiently rapid intracerebral bleeding can dissect fragments of cerebrum and displace them long distances across the tentorial opening.


Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1311
Author(s):  
Faraz Ahmad ◽  
Ping Liu

Lead (Pb) neurotoxicity is a major concern, particularly in children. Developmental exposure to Pb can alter neurodevelopmental trajectory and has permanent neuropathological consequences, including an increased vulnerability to further stressors. Ascorbic acid is among most researched antioxidant nutrients and has a special role in maintaining redox homeostasis in physiological and physio-pathological brain states. Furthermore, because of its capacity to chelate metal ions, ascorbic acid may particularly serve as a potent therapeutic agent in Pb poisoning. The present review first discusses the major consequences of Pb exposure in children and then proceeds to present evidence from human and animal studies for ascorbic acid as an efficient ameliorative supplemental nutrient in Pb poisoning, with a particular focus on developmental Pb neurotoxicity. In doing so, it is hoped that there is a revitalization for further research on understanding the brain functions of this essential, safe, and readily available vitamin in physiological states, as well to justify and establish it as an effective neuroprotective and modulatory factor in the pathologies of the nervous system, including developmental neuropathologies.


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