SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in Different Brain Pathologies
Mol Neurobiol. 2017-09-23; 55(7): 5439-5452
DOI: 10.1007/s12035-017-0762-5
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1. Mol Neurobiol. 2018 Jul;55(7):5439-5452. doi: 10.1007/s12035-017-0762-5. Epub
2017 Sep 23.
SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in
Different Brain Pathologies.
Salazar K(1)(2), Martínez F(1)(2), Pérez-Martín M(3), Cifuentes M(3), Trigueros
L(1)(3), Ferrada L(1), Espinoza F(1), Saldivia N(1), Bertinat R(1), Forman K(1),
Oviedo MJ(1), López-Gambero AJ(3), Bonansco C(4), Bongarzone ER(5)(6), Nualart
F(7)(8).
Author information:
(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.
(2)Departamento de Biología Celular, Facultad de Ciencias Biológicas,
Universidad de Concepción, Casilla 160-C, Concepcion, Chile.
(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.
(4)Centro de Neurobiología y Plasticidad Cerebral (CNPC), Instituto de
Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Gran Bretaña
Avenida 1111, 2360102, Valparaíso, Chile.
(5)Department of Anatomy and Cell Biology, College of Medicine, University of
Illinois Chicago, Chicago, IL, USA.
(6)Departamento de Química Biológica, Facultad de Farmacia y Bioquímica,
Universidad de Buenos Aires, Buenos Aires, Argentina.
(7)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. .
(8)Departamento de Biología Celular, Facultad de Ciencias Biológicas,
Universidad de Concepción, Casilla 160-C, Concepcion, Chile. .
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).
DOI: 10.1007/s12035-017-0762-5
PMID: 28942474 [Indexed for MEDLINE]