Vitamin C Transporter (SVCT2) Distribution in Developing and Adult Brains

Vitamin C is the major antioxidant molecule in the central nervous system (CNS), reaching concentrations of 10 mM in neurons and 400 μM in the cerebrospinal fluid (CSF). Uptake of vitamin C by brain cells is performed through the co‐transporter of ascorbic acid and sodium isoform 2, SVCT2, which is expressed in cells from the choroid plexus, neurons, oligodendrocytes, and ependymal cells. SVCT2 expression has also been described in cells at the neurogenic niche, specifically in proliferative type C cells. In this chapter, we will describe recently published studies of SVCT2 expression during brain development and define its polarization in cells from the radial glia (neuronal precursors within the CNS) and vitamin C‐mediated effects in regulating genes associated with the maintenance of CNS stem cell pluripotency. We will discuss the differential biological effect that vitamin C generates in neurons versus astrocytes and how the oxidized form of vitamin C, dehydroascorbic acid (DHA), produced by neurons in conditions of oxidative stress must leave this cell to be incorporated by astrocytes. In this context, we will discuss recent literature, which shows that DHA regulates glycolytic metabolism in neurons. In parallel, we will analyze vitamin C recycling by astrocytes, which reduce DHA into ascorbic acid (AA), increasing the antioxidant potential of the brain. Data discussed in this chapter will provide an updated view of SVCT2 distribution in the brain and will also describe how vitamin C recycling participates in normal or pathological brain function

Vitamin C controls neuronal necroptosis under oxidative stress

Under physiological conditions, vitamin C is the main antioxidant found in the central nervous system and is found in two states: reduced as ascorbic acid (AA) and oxidized as dehydroascorbic acid (DHA). However, under pathophysiological conditions, AA is oxidized to DHA. The oxidation of AA and subsequent production of DHA in neurons are associated with a decrease in GSH concentrations, alterations in glucose metabolism and neuronal death. To date, the endogenous molecules that act as intrinsic regulators of neuronal necroptosis under conditions of oxidative stress are unknown. Here, we show that treatment with AA regulates the expression of pro- and antiapoptotic genes. Vitamin C also regulates the expression of RIPK1/MLKL, whereas the oxidation of AA in neurons induces morphological alterations consistent with necroptosis and MLKL activation. The activation of necroptosis by AA oxidation in neurons results in bubble formation, loss of membrane integrity, and ultimately, cellular explosion. These data suggest that necroptosis is a target for cell death induced by vitamin C

Clinical prevalence of drooling in infant cerebral palsy

Objective: To determine the prevalence and severity of drooling in infant cerebral palsy (ICP) and analyze the possible surgical, pharmacological, myofunctional and novel alternative approaches to treatment of this disorder. Methods: A clinical study is made of a group of patients with ICP (cohort) and aged between 4 and 34 years, visiting a dental clinic for disabled patients. The classification of Thomas-Stonell and Greenberg was used to assess the presence and severity of drooling. Results: Of the total of 50 patients evaluated (52% males and 48% females), 58% presented drooling (mild in 44.4% and moderate to severe in 27.7%). Conclusion: Over half of the patients with ICP presented drooling. Effective options are therefore needed for the treatment of this problem, which poses a series of negative effects for both patients and their care givers

Periodontal disease associated to systemic genetic disorders

A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis ? in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefèvre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefèvre syndrome, where an established treatment protocol is available

Vitamin C Deficiency Reduces Neurogenesis and Proliferation in the SVZ and Lateral Ventricle Extensions of the Young Guinea Pig Brain

Although scurvy, the severe form of vitamin C deficiency, has been almost eradicated, the prevalence of subclinical vitamin C deficiency is much higher than previously estimated and its impact on human health might not be fully understood. Vitamin C is an essential molecule, especially in the central nervous system where it performs numerous, varied and critical functions, including modulation of neurogenesis and neuronal differentiation. Although it was originally considered to occur only in the embryonic brain, it is now widely accepted that neurogenesis also takes place in the adult brain. The subventricular zone (SVZ) is the neurogenic niche where the largest number of new neurons are born; however, the effect of vitamin C deficiency on neurogenesis in this key region of the adult brain is unknown. Therefore, through BrdU labeling, immunohistochemistry, confocal microscopy and transmission electron microscopy, we analyzed the proliferation and cellular composition of the SVZ and the lateral ventricle (LVE) of adult guinea pigs exposed to a vitamin-C-deficient diet for 14 and 21 days. We found that neuroblasts in the SVZ and LVE were progressively and significantly decreased as the days under vitamin C deficiency elapsed. The neuroblasts in the SVZ and LVE decreased by about 50% in animals with 21 days of deficiency; this was correlated with a reduction in BrdU positive cells in the SVZ and LVE. In addition, the reduction in neuroblasts was not restricted to a particular rostro–caudal area, but was observed throughout the LVE. We also found that vitamin C deficiency altered cellular morphology at the ultrastructural level, especially the cellular and nuclear morphology of ependymal cells of the LVE. (...)“This research was funded by FONDECYT, grant number 1221147 (to Francisco Nualart)”, “FONDECYT grant number 11170959 (to Nery Jara)”, “CONICYT-PIA, grant number ECM-12 (to Francisco Nualart)” and “FEDER-Andalucía, grant number UMA20-FEDERJA-112”. Partial funding for open access charge: Universidad de Málag

The biological basis of smoltification in Atlantic salmon

Chile is the second-largest producer of Atlantic salmon in the world, and the Chilean salmon production accounts for 27% of the world’s production. One important step of the productive cycle in freshwater is the smoltification process that prepares the fish for the marine life stage. This review describes the biological basis of smoltification in Atlantic salmon, with particular attention on branchial osmoregulatory adaptations. We also discuss some of the infectious diseases and problems in smoltification (two of the main causes of losses in Chilean aquaculture) that could be related from a physiological point of view

Preclinical and clinical studies for sodium tungstate: application in humans.

Diabetes is a complex metabolic disorder triggered by the deficient secretion of insulin by the pancreatic β-cell or the resistance of peripheral tissues to the action of the hormone. Chronic hyperglycemia is the major consequence of this failure, and also the main cause of diabetic problems. Indeed, several clinical trials have agreed in that tight glycemic control is the best way to stop progression of the disease. Many anti-diabetic drugs for treatment of type 2 diabetes are commercially available, but no ideal normoglycemic agent has been developed yet. Moreover, weight gain is the most common side effect of many oral anti-diabetic agents and insulin, and increased weight has been shown to worsen glycemic control and increase the risk of diabetes progression. In this sense, the inorganic salt sodium tungstate (NaW) has been studied in different animal models of metabolic syndrome and diabetes, proving to have a potent effect on normalizing blood glucose levels and reducing body weight, without any hypoglycemic action. Although the liver has been studied as the main site of NaW action, positive effects have been also addressed in muscle, pancreas, brain, adipose tissue and intestine, explaining the effective anti-diabetic action of this salt. Here, we review NaW research to date in these different target organs. We believe that NaW deserves more attention, since all available anti-diabetic treatments remain suboptimal and new therapeutics are urgently needed

Glial glucokinase expression in adult and post-natal development of the hypothalamic region

It has recently been proposed that hypothalamic glial cells sense glucose levels and release lactate as a signal to activate adjacent neurons. GK (glucokinase), the hexokinase involved in glucose sensing in pancreatic β-cells, is also expressed in the hypothalamus. However, it has not been clearly determined if glial and/or neuronal cells express this protein. Interestingly, tanycytes, the glia that cover the ventricular walls of the hypothalamus, are in contact with CSF (cerebrospinal fluid), the capillaries of the arcuate nucleus and adjacent neurons; this would be expected for a system that can detect and communicate changes in glucose concentration. Here, we demonstrated by Western-blot analysis, QRT–PCR [quantitative RT–PCR (reverse transcription–PCR)] and in situ hybridization that GK is expressed in tanycytes. Confocal microscopy and immunoultrastructural analysis revealed that GK is localized in the nucleus and cytoplasm of β1-tanycytes. Furthermore, GK expression increased in these cells during the second week of post-natal development. Based on this evidence, we propose that tanycytes mediate, at least in part, the mechanism by which the hypothalamus detects changes in glucose concentrations

The recent neophyte Opuntia aurantiaca Lindl.: distribution and potential invasion in Spain

Trabajo presentado en el XVI Optima Meeting (Organization for the Phyto-Taxonomic Investigation of the Mediterranean Area), celebrado en Atenas (Grecia), del 2 al 5 de octubre de 2019The Cactaceae, and especially its most emblematic genus, Opuntia, have become one of the groups of plants with greater invasion potential in Spain. In fact, this area is considered one of the three global hotspots of invasion of cacti, together with South Africa and Australia. In our country, one of the most recently detected species is Opuntia aurantiaca Lindl, a small cactus with an enormous capacity of dispersion by means of cladodes and (sterile) fruits, which are easily detached and adhere to animals, clothes, and footwear. Probably native to the Southern Cone (Argentina and Uruguay), it behaves as a very aggressive invader in Australia and South Africa. In Europe, it only occurs on the Mediterranean coast of the Iberian Peninsula (Catalonia and Valencian Community). In this study, the geographic range of the species is updated at the peninsular level. Firstly detected at the beginning of the last decade in Navajas (Castellón), it has been subsequently observed in other places of the province of Castellón, but also in Valencia, Tarragona and Barcelona. With all occurrence data, its potential distribution is estimated using the algorithm of maximum entropy implemented in the program MaxEnt. Distribution models are built for the current climatic conditions as well as for different scenarios of global warming. Due to its possible invasive nature, it is necessary to eradicate the existing populations at this initial stage. Legislation should consider the prohibition of trade and transport of this plant to avoid new introductions