Immunohistochemical study of the distribution of sodium‐dependent vitamin C transporters in adult rat brain

Mun, Ga Hee; Kim, Myeung Ju; Lee, Ju Hyun; Kim, Hyun Jun; Chung, Yoon Hee; Chung, Young Bae; Kang, Jae Seung; Hwang, Young Il; Oh, Seung Ha; Kim, Joong Gon; Hwang, Dong Soo; Shin, Dong Hoon; Lee, Wang Jae

doi:10.1002/jnr.20751

Cited by 74 publications

(87 citation statements)

References 31 publications

(52 reference statements)

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“…Recently, several studies revealed the expression and transport activity of SVCT2 in a variety of nervous system compartments and cell types (Castro et al, 2001;Angelow et al, 2003;Garcia Mde et al, 2005;Mun et al, 2006;Qiu et al, 2007;Caprile et al, 2009;Harrison and May, 2009;Gess et al, 2011). We previously showed expression and activity of SVCT2 in Schwann cell cultures in vitro (Gess et al, 2010).…”

Section: Discussionmentioning

confidence: 88%

Sodium-Dependent Vitamin C Transporter 2 Deficiency Causes Hypomyelination and Extracellular Matrix Defects in the Peripheral Nervous System

Gess¹,

Röhr²,

Fledrich³

et al. 2011

J. Neurosci.

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Ascorbic acid (vitamin C) is necessary for myelination of Schwann cell/neuron cocultures and has shown beneficial effects in the treatment of a Charcot-Marie-Tooth neuropathy 1A (CMT1A) mouse model. Although clinical studies revealed that ascorbic acid treatment had no impact on CMT1A, it is assumed to have an important function in peripheral nerve myelination and possibly in remyelination. However, the transport pathway of ascorbic acid into peripheral nerves and the mechanism of ascorbic acid function in peripheral nerves in vivo remained unclear.In this study, we used sodium-dependent vitamin C transporter 2-heterozygous (SVCT2 ϩ/Ϫ ) mice to elucidate the functions of SVCT2 and ascorbic acid in the murine peripheral nervous system. SVCT2 and ascorbic acid levels were reduced in SVCT2 ϩ/Ϫ peripheral nerves. Morphometry of sciatic nerve fibers revealed a decrease in myelin thickness and an increase in G-ratios in SVCT2ϩ/Ϫ mice. Nerve conduction velocities and sensorimotor performance in functional tests were reduced in SVCT2 ϩ/Ϫ mice. To investigate the mechanism of ascorbic acid function, we studied the expression of collagens in the extracellular matrix of peripheral nerves. Here, we show that expression of various collagen types was reduced in sciatic nerves of SVCT2 ϩ/Ϫ mice. We found that collagen gene transcription was reduced in SVCT2 ϩ/Ϫ mice but hydroxyproline levels were not, indicating that collagen formation was regulated on the transcriptional and not the posttranslational level. These results help to clarify the transport pathway and mechanism of action of ascorbic acid in the peripheral nervous system and may lead to novel therapeutic approaches to peripheral neuropathies by manipulation of SVCT2 function.

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Section: Discussionmentioning

confidence: 88%

Sodium-Dependent Vitamin C Transporter 2 Deficiency Causes Hypomyelination and Extracellular Matrix Defects in the Peripheral Nervous System

Gess¹,

Röhr²,

Fledrich³

et al. 2011

J. Neurosci.

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show abstract

“…Many studies indicate that SVCT2 is a transporter that is preferentially expressed in neurons from different areas in the adult brain, such as the cortex, hippocampus, hypothalamus, and cerebellar precursors [1,[7][8][9][10][11]. SVCT2 mediates uptake of AA, an important molecule for antioxidant defense and general metabolic needs of neurons.…”

Section: Distribution and Function Of Svct2 In The Adult Brainmentioning

confidence: 99%

“…Although SVCT2 was originally thought to be a neuronal transporter, there is increasing evidence demonstrating its expression in glial cells in the CNS [4,7,8,10,[12][13][14]. Indeed, SVCT2 has been reported in cortical microglia, where its function remains unknown [10]. In hypothalamic tanycytes, it may participate in maintaining the high parenchymal concentrations of vitamin C that characterize this region [8].…”

Section: Distribution and Function Of Svct2 In The Adult Brainmentioning

confidence: 99%

“…In hypothalamic tanycytes, it may participate in maintaining the high parenchymal concentrations of vitamin C that characterize this region [8]. Furthermore, in choroid plexus cells, it facilitates entry of AA into the brain through the blood-cerebrospinal fluid (CSF) barrier [4,7,10,12]. In Schwann cells, SVCT2 promotes axonal myelination in the peripheral nervous system [14].…”

Section: Distribution and Function Of Svct2 In The Adult Brainmentioning

confidence: 99%

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

Ferrada¹,

Salazar²,

Santander³

2017

Vitamin C

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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.

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“…SVCT2 proteininin erişkin sıçan beynindeki dağılımının incelendiği bir immünhistokimya çalışmasında ise protein yoğunluğunun serebral kortekste, hipokampusta ve serebellumda Purkinje hücrelerinde yoğun olduğu görülmüştür. [51] Diğer yandan hipokampal nö-ron kültüründe yapılan bir immünhistokimya çalışmasında SVCT2 boyanma-sının nöronların aksonlarında yoğunluk kazandığı gösterilerek, SVCT2' nin aksonal taşıyıcı ailesine ait olduğu iddia edilmiştir. SVCT2, nöronlardaki askorbik asit içeriğinin idamesini sağlayarak nöronal gelişimde ve nöronal işlevlerin matürasyonunda, eksitotoksisite ve oksidatif stresten korunmada önemli rol oynamaktadır.…”

Section: Sinyal Yolaklarının Psikiyatrik Hastalıkların Patogenezindekunclassified

Antioxidant Vitamins and Their Use in Psychiatry

Mazlum

2012

Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychia

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ÖZETOksidatif stres, vücut metabolizması sırasında üretilen serbest radikaller ve bunların vücuttan temizlenmesi ile ilgili antioksidan sistem elemanları arasın-daki dengenin serbest radikaller lehine bozulması durumudur. Kanser, kardiyovasküler hastalıklar ve nörodejeneratif hastalıkların etiyolojisinde etkili olduğu düşünülen oksidatif stres, aynı zamanda şizofreni, duygudurum bozuklukları, otizm, dikkat eksikliği hiperaktivite bozukluğu gibi bazı ruhsal bozuklukların patogenezinde de sorumlu mekanizmalardan birisi olarak gö-rülmektedir. Bu bağlamda ruhsal bozuklukların bilinen mevcut tedavileri dışında antioksidan vitamin ekleme tedavileri gündeme gelmiştir. Bu süreçte yer alan A, C ve E vitaminleri antioksidan savunmayı desteklemek dışında bazı ruhsal bozukluklarda görülebilen beslenme sorunlarına ikincil eksikliklerde de kullanılabilmektedir. Bu yazıda A, C ve E vitaminlerinin vücuttaki süreçlerine ilişkin biyokimyasal, moleküler ve genetik veriler gözden geçirile-cek daha sonra antioksidan vitaminlerin ekleme tedavilerinin psikiyatride hangi koşullarda gündeme gelebileceği ve uygulanması halinde dikkat edilmesi gereken faktörler tartışılacaktır. Anahtar Sözcükler: Vitamin A, vitamin E, askorbik asid ABSTRACTOxidative stress can be defined as imbalance between prooxidant molecules produced during body metabolism and members of antioxidant system for favor of former. Oxidative stress, which is included in the pathogenesis of cancer, aging, cardiovascular and neurodegenerative disorders, is also considered for pathogenetic mechanisms underlying psychiatric disorders including schizophrenia, mood disorders, attention deficit hyperactivity disorder. Due to important role of antioxidant vitamins in antioxidant defense mechanisms, vitamin supplementation therapies are considered in addition to conventional

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Immunohistochemical study of the distribution of sodium‐dependent vitamin C transporters in adult rat brain

Cited by 74 publications

References 31 publications

Sodium-Dependent Vitamin C Transporter 2 Deficiency Causes Hypomyelination and Extracellular Matrix Defects in the Peripheral Nervous System

Sodium-Dependent Vitamin C Transporter 2 Deficiency Causes Hypomyelination and Extracellular Matrix Defects in the Peripheral Nervous System

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

Antioxidant Vitamins and Their Use in Psychiatry

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