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SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in Different Brain Pathologies

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Abstract

Ascorbic acid (AA), the reduced form of vitamin C, acts as a neuroprotector by eliminating free radicals in the brain. Sodium/vitamin C co-transporter isoform 2 (SVCT2) mediates uptake of AA by neurons. It has been reported that SVCT2 mRNA is induced in astrocytes under ischemic damage, suggesting that its expression is enhanced in pathological conditions. However, it remains to be established if SVCT expression is altered in the presence of reactive astrogliosis generated by different brain pathologies. In the present work, we demonstrate that SVCT2 expression is increased in astrocytes present at sites of neuroinflammation induced by intracerebroventricular injection of a GFP-adenovirus or the microbial enzyme, neuraminidase. A similar result was observed at 5 and 10 days after damage in a model of traumatic injury and in the hippocampus and cerebral cortex in the in vivo kindling model of epilepsy. Furthermore, we defined that cortical astrocytes maintained in culture for long periods acquire markers of reactive gliosis and express SVCT2, in a similar way as previously observed in situ. Finally, by means of second harmonic generation and 2-photon fluorescence imaging, we analyzed brain necropsied material from patients with Alzheimer’s disease (AD), which presented with an accumulation of amyloid plaques. Strikingly, although AD is characterized by focalized astrogliosis surrounding amyloid plaques, SVCT2 expression at the astroglial level was not detected. We conclude that SVCT2 is heterogeneously induced in reactive astrogliosis generated in different pathologies affecting the central nervous system (CNS).

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Acknowledgements

This work was partially supported by a FONDECYT grant 1140477 and CONICYT PIA ECM-12 grant (both to Francisco Nualart), the National Institutes of Health grant (R01 NS065808) to Ernesto R. Bongarzone, grants 1130491 from FONDECYT, CONICYT-Chile, and CID 1/2006 from DIPUV to Christian Bonansco, Fondecyt grant 11140405 to Katterine Salazar and Fondecyt grant 11150678 to Fernando Martínez. The funders had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript. We thank Ms. Ximena Koch for technical support.

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  1. Katterine Salazar and Fernando Martínez contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Neurobiology and Stem Cells NeuroCellT, Department of Cellular Biology, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepcion, Chile

    Katterine Salazar, Fernando Martínez, Laura Trigueros, Luciano Ferrada, Francisca Espinoza, Natalia Saldivia, Romina Bertinat, Katherine Forman, María José Oviedo & Francisco Nualart

  2. Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Casilla 160-C, Concepcion, Chile

    Katterine Salazar, Fernando Martínez & Francisco Nualart

  3. Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, BIONAND, Andalusian Center for Nanomedicine and Biotechnology and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain

    Margarita Pérez-Martín, Manuel Cifuentes, Laura Trigueros & Antonio J. López-Gambero

  4. Centro de Neurobiología y Plasticidad Cerebral (CNPC), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Gran Bretaña Avenida 1111, 2360102, Valparaíso, Chile

    Christian Bonansco

  5. Department of Anatomy and Cell Biology, College of Medicine, University of Illinois Chicago, Chicago, IL, USA

    Ernesto R. Bongarzone

  6. Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Ernesto R. Bongarzone

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  1. Katterine Salazar
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Salazar, K., Martínez, F., Pérez-Martín, M. et al. SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in Different Brain Pathologies. Mol Neurobiol 55, 5439–5452 (2018). https://doi.org/10.1007/s12035-017-0762-5

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