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Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts.

Nualart F, Mack L, García A, Cisternas P, Bongarzone ER, Heitzer M, Jara N, Martínez F, Ferrada L, Espinoza F, Baeza V, Salazar K - J Stem Cell Res Ther (2014)

Bottom Line: After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation.Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region.Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Center for Advanced Microscopy CMA BIO-BIO, Neurobiology and Stem cell Laboratory, Concepcion University, Chile.

ABSTRACT
Vitamin C is an essential micronutrient in the human diet; its deficiency leads to a number of symptoms and ultimately death. After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation. In this review, we will compare the molecular and structural aspects of vitamin C and glucose transporters and their expression in endothelial or choroid plexus cells, which form part of the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, respectively. Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region. Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

No MeSH data available.


Related in: MedlinePlus

Tanycyte distribution and SVCT2 immunoreaction in hypothalamic cellsTanycytes are specialized hypothalamic glial cells that can be classified as alpha and beta-tanycytes. The tanycytes located in the dorsal walls of the third ventricle are classified as alpha tanycytes, which are involved in neurogenic activity (stem-like cells). Beta-1 tanycytes are located in the lateral lower area of the ventricle and develop elongated cell processes that form a bow through the arcuate nucleus and reach the lateral sulcus of the infundibular region in the lateral hypothalamus. A. SVCT2 and B. vimentin expression analysis in hypothalamic alpha and beta tanycytes. Detailed tanycyte structure and vimentin immunoreaction are observed in C and D. The fluorescence analysis of vimentin (red) and nuclei (Topro in blue) was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning, Z-stack imaging and rendering analysis (process of generating an image from a model). E–G. Alpha-tanycyte distribution after infection with adenovirus-GFP (E) or fluorescence analysis of vimentin (F) and SVCT2 (G). IIIV, Third ventricle; AN, Arcuate nucleus; ME, Median eminence. Scale bars in A and B, 800 μm; in C and D 400 μm; and in E–G, 200 μm.
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Figure 3: Tanycyte distribution and SVCT2 immunoreaction in hypothalamic cellsTanycytes are specialized hypothalamic glial cells that can be classified as alpha and beta-tanycytes. The tanycytes located in the dorsal walls of the third ventricle are classified as alpha tanycytes, which are involved in neurogenic activity (stem-like cells). Beta-1 tanycytes are located in the lateral lower area of the ventricle and develop elongated cell processes that form a bow through the arcuate nucleus and reach the lateral sulcus of the infundibular region in the lateral hypothalamus. A. SVCT2 and B. vimentin expression analysis in hypothalamic alpha and beta tanycytes. Detailed tanycyte structure and vimentin immunoreaction are observed in C and D. The fluorescence analysis of vimentin (red) and nuclei (Topro in blue) was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning, Z-stack imaging and rendering analysis (process of generating an image from a model). E–G. Alpha-tanycyte distribution after infection with adenovirus-GFP (E) or fluorescence analysis of vimentin (F) and SVCT2 (G). IIIV, Third ventricle; AN, Arcuate nucleus; ME, Median eminence. Scale bars in A and B, 800 μm; in C and D 400 μm; and in E–G, 200 μm.

Mentions: AA concentrations vary within the brain; higher AA concentrations are consistently observed in the hippocampus and hypothalamus compared with other structures within the CNS [69]. In the hypothalamus, vitamin C modulates nitric oxide neurotransmission [70]. Tanycytes are specialized hypothalamic glial cells localized in circumventricular organs, such as the median eminence (Figure 3) [71–74]. Tanycytes are classified into at least four types, alpha1, alpha 2, beta1, and beta 2, and immunofluorescence analyses revealed the strongest immunoreaction for SVCT2 in β1 and β2 tanycytes [65]. Ultrastructural immunohistochemistry confirmed that SVCT2 was localized in the cellular membranes of the apical microvilli and blebs of β1 tanycytes, and AA transport by SVCT2 within these cells was confirmed using primary cultures of tanycytes, demonstrating that AA transport within these cells is Na+ dependent and unaffected by CytB, a GLUT inhibitor [65]. In this report, we used spectral confocal microscopy, z-stack projection and 3D rendering analysis to confirm SVCT2 expression in alpha and beta hypothalamic tanycytes (Figure 3A and 3G), which also showed an intense immunoreaction for vimentin (Figure 3B–3D and 3F). These cells were also identified using an adenovirus expressing enhanced green fluorescence protein (EGFP; Figure 3E). SVCT2 was not detected in hypothalamic astrocytes, which presented high GFAP expression (Figure 4A–D); its expression was also absent in endothelial cells and hypothalamic neurons (Figure 4). SVCT2 expression in tanycytes and the high concentration of AA in the hypothalamus suggest a neuroprotective mechanism for concentrating vitamin C in this specific area of the brain that is in contact with the CSF and blood vessels.


Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts.

Nualart F, Mack L, García A, Cisternas P, Bongarzone ER, Heitzer M, Jara N, Martínez F, Ferrada L, Espinoza F, Baeza V, Salazar K - J Stem Cell Res Ther (2014)

Tanycyte distribution and SVCT2 immunoreaction in hypothalamic cellsTanycytes are specialized hypothalamic glial cells that can be classified as alpha and beta-tanycytes. The tanycytes located in the dorsal walls of the third ventricle are classified as alpha tanycytes, which are involved in neurogenic activity (stem-like cells). Beta-1 tanycytes are located in the lateral lower area of the ventricle and develop elongated cell processes that form a bow through the arcuate nucleus and reach the lateral sulcus of the infundibular region in the lateral hypothalamus. A. SVCT2 and B. vimentin expression analysis in hypothalamic alpha and beta tanycytes. Detailed tanycyte structure and vimentin immunoreaction are observed in C and D. The fluorescence analysis of vimentin (red) and nuclei (Topro in blue) was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning, Z-stack imaging and rendering analysis (process of generating an image from a model). E–G. Alpha-tanycyte distribution after infection with adenovirus-GFP (E) or fluorescence analysis of vimentin (F) and SVCT2 (G). IIIV, Third ventricle; AN, Arcuate nucleus; ME, Median eminence. Scale bars in A and B, 800 μm; in C and D 400 μm; and in E–G, 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126260&req=5

Figure 3: Tanycyte distribution and SVCT2 immunoreaction in hypothalamic cellsTanycytes are specialized hypothalamic glial cells that can be classified as alpha and beta-tanycytes. The tanycytes located in the dorsal walls of the third ventricle are classified as alpha tanycytes, which are involved in neurogenic activity (stem-like cells). Beta-1 tanycytes are located in the lateral lower area of the ventricle and develop elongated cell processes that form a bow through the arcuate nucleus and reach the lateral sulcus of the infundibular region in the lateral hypothalamus. A. SVCT2 and B. vimentin expression analysis in hypothalamic alpha and beta tanycytes. Detailed tanycyte structure and vimentin immunoreaction are observed in C and D. The fluorescence analysis of vimentin (red) and nuclei (Topro in blue) was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning, Z-stack imaging and rendering analysis (process of generating an image from a model). E–G. Alpha-tanycyte distribution after infection with adenovirus-GFP (E) or fluorescence analysis of vimentin (F) and SVCT2 (G). IIIV, Third ventricle; AN, Arcuate nucleus; ME, Median eminence. Scale bars in A and B, 800 μm; in C and D 400 μm; and in E–G, 200 μm.
Mentions: AA concentrations vary within the brain; higher AA concentrations are consistently observed in the hippocampus and hypothalamus compared with other structures within the CNS [69]. In the hypothalamus, vitamin C modulates nitric oxide neurotransmission [70]. Tanycytes are specialized hypothalamic glial cells localized in circumventricular organs, such as the median eminence (Figure 3) [71–74]. Tanycytes are classified into at least four types, alpha1, alpha 2, beta1, and beta 2, and immunofluorescence analyses revealed the strongest immunoreaction for SVCT2 in β1 and β2 tanycytes [65]. Ultrastructural immunohistochemistry confirmed that SVCT2 was localized in the cellular membranes of the apical microvilli and blebs of β1 tanycytes, and AA transport by SVCT2 within these cells was confirmed using primary cultures of tanycytes, demonstrating that AA transport within these cells is Na+ dependent and unaffected by CytB, a GLUT inhibitor [65]. In this report, we used spectral confocal microscopy, z-stack projection and 3D rendering analysis to confirm SVCT2 expression in alpha and beta hypothalamic tanycytes (Figure 3A and 3G), which also showed an intense immunoreaction for vimentin (Figure 3B–3D and 3F). These cells were also identified using an adenovirus expressing enhanced green fluorescence protein (EGFP; Figure 3E). SVCT2 was not detected in hypothalamic astrocytes, which presented high GFAP expression (Figure 4A–D); its expression was also absent in endothelial cells and hypothalamic neurons (Figure 4). SVCT2 expression in tanycytes and the high concentration of AA in the hypothalamus suggest a neuroprotective mechanism for concentrating vitamin C in this specific area of the brain that is in contact with the CSF and blood vessels.

Bottom Line: After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation.Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region.Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Center for Advanced Microscopy CMA BIO-BIO, Neurobiology and Stem cell Laboratory, Concepcion University, Chile.

ABSTRACT
Vitamin C is an essential micronutrient in the human diet; its deficiency leads to a number of symptoms and ultimately death. After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation. In this review, we will compare the molecular and structural aspects of vitamin C and glucose transporters and their expression in endothelial or choroid plexus cells, which form part of the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, respectively. Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region. Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions.

No MeSH data available.


Related in: MedlinePlus