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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

SVCT2 is highly expressed in hypothalamic tanycytesTanycytes and astrocytes are specialized glial cells distributed in the hypothalamus. Tanycytes can be classified as alpha (A–B) or beta (C–D), which contact the CSF of the third ventricle (apical area); the processes contact different areas of the hypothalamic region (basal area). Astrocytes are present in the hypothalamic sub-ependymal region and are concentrated in the median eminence (C, light-blue staining) below the ventricular layer (beta-2 tanycytes). SVCT2 and GFAP immunofluorescence analysis was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning and Z-stack projection imaging. An intense immunoreaction for SVCT2 was detected in alpha and beta tanycytes (red signal); however, astrocytes, endothelial cells, and neurons were negative for SVCT2 staining. Astrocytes showed an intense immunoreaction for GFAP (light-blue staining). IIIV, Third ventricle; AN, Arcuate nucleus; GFAP, glial fibrillary acidic protein; ME, Median eminence; pT, Pars tuberalis. Scale bars in A and C, 500 μm; in B and D, 40 μm.
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Figure 4: SVCT2 is highly expressed in hypothalamic tanycytesTanycytes and astrocytes are specialized glial cells distributed in the hypothalamus. Tanycytes can be classified as alpha (A–B) or beta (C–D), which contact the CSF of the third ventricle (apical area); the processes contact different areas of the hypothalamic region (basal area). Astrocytes are present in the hypothalamic sub-ependymal region and are concentrated in the median eminence (C, light-blue staining) below the ventricular layer (beta-2 tanycytes). SVCT2 and GFAP immunofluorescence analysis was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning and Z-stack projection imaging. An intense immunoreaction for SVCT2 was detected in alpha and beta tanycytes (red signal); however, astrocytes, endothelial cells, and neurons were negative for SVCT2 staining. Astrocytes showed an intense immunoreaction for GFAP (light-blue staining). IIIV, Third ventricle; AN, Arcuate nucleus; GFAP, glial fibrillary acidic protein; ME, Median eminence; pT, Pars tuberalis. Scale bars in A and C, 500 μm; in B and D, 40 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)

SVCT2 is highly expressed in hypothalamic tanycytesTanycytes and astrocytes are specialized glial cells distributed in the hypothalamus. Tanycytes can be classified as alpha (A–B) or beta (C–D), which contact the CSF of the third ventricle (apical area); the processes contact different areas of the hypothalamic region (basal area). Astrocytes are present in the hypothalamic sub-ependymal region and are concentrated in the median eminence (C, light-blue staining) below the ventricular layer (beta-2 tanycytes). SVCT2 and GFAP immunofluorescence analysis was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning and Z-stack projection imaging. An intense immunoreaction for SVCT2 was detected in alpha and beta tanycytes (red signal); however, astrocytes, endothelial cells, and neurons were negative for SVCT2 staining. Astrocytes showed an intense immunoreaction for GFAP (light-blue staining). IIIV, Third ventricle; AN, Arcuate nucleus; GFAP, glial fibrillary acidic protein; ME, Median eminence; pT, Pars tuberalis. Scale bars in A and C, 500 μm; in B and D, 40 μm.
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Related In: Results  -  Collection

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Show All Figures
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Figure 4: SVCT2 is highly expressed in hypothalamic tanycytesTanycytes and astrocytes are specialized glial cells distributed in the hypothalamus. Tanycytes can be classified as alpha (A–B) or beta (C–D), which contact the CSF of the third ventricle (apical area); the processes contact different areas of the hypothalamic region (basal area). Astrocytes are present in the hypothalamic sub-ependymal region and are concentrated in the median eminence (C, light-blue staining) below the ventricular layer (beta-2 tanycytes). SVCT2 and GFAP immunofluorescence analysis was performed using confocal spectral microscopy (Zeiss 780 equipment), tile scanning and Z-stack projection imaging. An intense immunoreaction for SVCT2 was detected in alpha and beta tanycytes (red signal); however, astrocytes, endothelial cells, and neurons were negative for SVCT2 staining. Astrocytes showed an intense immunoreaction for GFAP (light-blue staining). IIIV, Third ventricle; AN, Arcuate nucleus; GFAP, glial fibrillary acidic protein; ME, Median eminence; pT, Pars tuberalis. Scale bars in A and C, 500 μm; in B and D, 40 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