SVCT2 Overexpression and Ascorbic Acid Uptake Increase Cortical Neuron Differentiation, Which Is Dependent on Vitamin C Recycling between Neurons and Astrocytes
| Autor: | Eder Ramírez, Rocío Magdalena, Katterine Salazar, Natalia Saldivia, María José Oviedo, Francisca Espinoza, Luciano Ferrada, Viviana Ulloa, Ninoschka Troncoso, María José Barahona, Fernando Martínez, Gustavo Cerda-Gallardo, Francisco Nualart |
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| Rok vydání: | 2021 |
| Předmět: |
Neurite
Physiology Clinical Biochemistry vitamin C RM1-950 neuronal branching Hippocampal formation Biochemistry Article SIM superresolution neurites chemistry.chemical_compound SVCT2 Neurosphere neurospheres medicine Molecular Biology biology dehydroascorbic acid cortical neurons Chemistry Glutamate receptor Cell Biology Ascorbic acid Cell biology medicine.anatomical_structure nervous system Cerebral cortex bystander effect biology.protein ascorbic acid GLUT1 Dehydroascorbic acid Therapeutics. Pharmacology vitamin C recycling |
| Zdroj: | Antioxidants Volume 10 Issue 9 Antioxidants, Vol 10, Iss 1413, p 1413 (2021) |
| ISSN: | 2076-3921 |
| Popis: | During brain development, sodium–vitamin C transporter (SVCT2) has been detected primarily in radial glial cells in situ, with low-to-absent expression in cerebral cortex neuroblasts. However, strong SVCT2 expression is observed during the first postnatal days, resulting in increased intracellular concentration of vitamin C. Hippocampal neurons isolated from SVCT2 knockout mice showed shorter neurites and low clustering of glutamate receptors. Other studies have shown that vitamin C-deprived guinea pigs have reduced spatial memory, suggesting that ascorbic acid (AA) and SVCT2 have important roles in postnatal neuronal differentiation and neurite formation. In this study, SVCT2 lentiviral overexpression induced branching and increased synaptic proteins expression in primary cultures of cortical neurons. Analysis in neuroblastoma 2a (Neuro2a) and human subventricular tumor C3 (HSVT-C3) cells showed similar branching results. SVCT2 was mainly observed in the cell membrane and endoplasmic reticulum however, it was not detected in the mitochondria. Cellular branching in neuronal cells and in a previously standardized neurosphere assay is dependent on the recycling of vitamin C or reduction in dehydroascorbic acid (DHA, produced by neurons) by glial cells. The effect of WZB117, a selective glucose/DHA transporter 1 (GLUT1) inhibitor expressed in glial cells, was also studied. By inhibiting GLUT1 glial cells, a loss of branching is observed in vitro, which is reproduced in the cerebral cortex in situ. We concluded that vitamin C recycling between neurons and astrocyte-like cells is fundamental to maintain neuronal differentiation in vitro and in vivo. The recycling activity begins at the cerebral postnatal cortex when neurons increase SVCT2 expression and concomitantly, GLUT1 is expressed in glial cells. |
| Databáze: | OpenAIRE |
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