SVCT2 transporter expression is post-natally induced in cortical neurons and its function is regulated by its short isoform

Salazar K1, Cerda G, Martínez F, Sarmiento JM, González C, Rodríguez F, García-Robles M, Tapia JC, Cifuentes M, Nualart F.

Abstract

Different studies have demonstrated the importance of micronutrients, such as vitamins, for normal adult brain function and development. Vitamin C is not synthesized in the brain, but high levels are detected in this organ because of the existence of specific uptake mechanisms, which concentrate ascorbic acid from the bloodstream to the cerebrospinal fluid and then into neurons and glial cells. Two different isoforms of sodium-vitamin C cotransporters (SVCT1 and SVCT2) have been cloned. SVCT2 expression has been observed in the adult hippocampus and cortical neurons by in situ hybridization. In addition, the localization of SVCT2 in the rat fetal brain has been studied by immunohistochemistry and in situ hybridization, demonstrating that SVCT2 is highly expressed in the ventricular and subventricular areas of the brain cortex. However, there are currently no immunohistochemical data regarding SVCT2 expression and function in the post-natal brain. Therefore, we analyzed SVCT2 expression in the developing brain cortex of mice, and demonstrated an increase in SVCT2 mRNA in mice at 1-15 days of age. The expression of a short isoform, SVCT2sh, was also detected within the same period. SVCT2 expression was concentrated in neurons within the inner layer of the brain cortex. Both SVCT2 isoforms were coexpressed in N2a cells to obtain functional data. Fluorescence resonance energy transfer analysis revealed a molecular interaction between SVCT2wt and SVCT2sh. Finally, differences in transport ratios suggested that SVCT2sh expression inhibited ascorbic acid uptake in N2a cells when both isoforms were coexpressed.

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Título según WOS: SVCT2 transporter expression is post-natally induced in cortical neurons and its function is regulated by its short isoform
Título según SCOPUS: SVCT2 transporter expression is post-natally induced in cortical neurons and its function is regulated by its short isoform
Título de la Revista: JOURNAL OF NEUROCHEMISTRY
Volumen: 130
Número: 5
Editorial: Wiley
Fecha de publicación: 2014
Página de inicio: 693
Página final: 706
Idioma: English
URL: http://doi.wiley.com/10.1111/jnc.12793
DOI:

10.1111/jnc.12793

Notas: ISI, SCOPUS - ISI