SVCT2 Is Expressed by Cerebellar Precursor Cells, Which Differentiate into Neurons in Response to Ascorbic Acid

Oyarce, Karina; Silva-Álvarez, Carmen; Ferrada, Luciano; Martínez, Fernando Martínez; Salazar, Katterine; Nualart, Francisco

doi:10.1007/s12035-016-0366-5

Cited by 18 publications

(35 citation statements)

References 45 publications

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“…Similar results were obtained by Oyarce et al. () in mouse Purkinje cells. Finally, in both species, strong immunostaining was observed in neurons of cortex and hippocampus, although the patterns were not perfectly aligned.…”

Section: Discussionsupporting

confidence: 91%

“…Conversely, no immunoreactivity was observed in the hypothalamus or the cerebellum in the present study, whereas intense SVCT2-IR was observed in many hypothalamic nuclei and in the Purkinje cell layer in the rat. Similar results were obtained by Oyarce et al (2017) in mouse Purkinje cells. Finally, in both species, strong immunostaining was observed in neurons of cortex and hippocampus, although the patterns were not perfectly aligned.…”

Section: Distribution Of Svct2supporting

confidence: 88%

“…; Oyarce et al. ). During aging, the expression of genes involved in stress‐response pathways increases.…”

Section: Discussionmentioning

confidence: 96%

“…Because allelic variations can alter the efficiency of the metabolic pathways that regulate vitamin storage and removal (Baxter et al 2012;Harrison et al 2014;Mocchegiani et al 2014), the genetic background of a model system is important. In fact, there is increasing interest in studies that explore the influence of gene expression on these two vitamins (Brigelius-Flohe, 2006;Harrison et al 2014;Mocchegiani et al 2014;Oyarce et al 2017). During aging, the expression of genes involved in stress-response pathways increases.…”

Section: Animal Model and Agingmentioning

confidence: 99%

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Vitamin transporters in mice brain with aging

et al. 2018

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Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann's glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.

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Section: Discussionsupporting

confidence: 91%

Section: Distribution Of Svct2supporting

confidence: 88%

“…; Oyarce et al. ). During aging, the expression of genes involved in stress‐response pathways increases.…”

Section: Discussionmentioning

confidence: 96%

Section: Animal Model and Agingmentioning

confidence: 99%

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Vitamin transporters in mice brain with aging

et al. 2018

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“…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%

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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Ascorbic acid and its transporter SVCT2, affect radial glia cells differentiation in postnatal stages

Saldivia,

Salazar,

Cifuentes

et al. 2024

Glia

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Radial glia (RG) cells generate neurons and glial cells that make up the cerebral cortex. Both in rodents and humans, these stem cells remain for a specific time after birth, named late radial glia (lRG). The knowledge of lRG and molecules that may be involved in their differentiation is based on very limited data. We analyzed whether ascorbic acid (AA) and its transporter SVCT2, are involved in lRG cells differentiation. We demonstrated that lRG cells are highly present between the first and fourth postnatal days. Anatomical characterization of lRG cells, revealed that lRG cells maintained their bipolar morphology and stem‐like character. When lRG cells were labeled with adenovirus‐eGFP at 1 postnatal day, we detected that some cells display an obvious migratory neuronal phenotype, suggesting that lRG cells continue generating neurons postnatally. Moreover, we demonstrated that SVCT2 was apically polarized in lRG cells. In vitro studies using the transgenic mice SVCT2+/− and SVCT2tg (SVCT2‐overexpressing mouse), showed that decreased SVCT2 levels led to accelerated differentiation into astrocytes, whereas both AA treatment and elevated SVCT2 expression maintain the lRG cells in an undifferentiated state. In vivo overexpression of SVCT2 in lRG cells generated cells with a rounded morphology that were migratory and positive for proliferation and neuronal markers. We also examined mediators that can be involved in AA/SVCT2‐modulated signaling pathways, determining that GSK3‐β through AKT, mTORC2, and PDK1 is active in brains with high levels of SVCT2/AA. Our data provide new insights into the role of AA and SVCT2 in late RG cells.

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SVCT2 Is Expressed by Cerebellar Precursor Cells, Which Differentiate into Neurons in Response to Ascorbic Acid

Cited by 18 publications

References 45 publications

Vitamin transporters in mice brain with aging

Vitamin transporters in mice brain with aging

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

Ascorbic acid and its transporter SVCT2, affect radial glia cells differentiation in postnatal stages

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