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

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).

• Authors: Katterine Salazar, Fernando Martínez, Margarita Pérez-Martín, Manuel Cifuentes, Laura Trigueros, Luciano Ferrada, Francisca Espinoza, Natalia Saldivia, Romina Bertinat, Katherine Forman, María José Oviedo, Antonio J López-Gambero, Christian Bonansco, Ernesto R Bongarzone, Francisco Nualart
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 55 Issue 7 Pg. 5439-5452 (Jul 2018) ISSN: 1559-1182 [Electronic] United States
• PMID: 28942474 (Publication Type: Journal Article)

Chemical References

• Slc23a2 protein, rat
• Sodium-Coupled Vitamin C Transporters
• Green Fluorescent Proteins
• Neuraminidase

Topics

• Adenoviridae (metabolism)
• Alzheimer Disease (metabolism, pathology)
• Animals
• Astrocytes (metabolism, pathology)
• Brain (metabolism, pathology)
• Gliosis (metabolism, pathology)
• Green Fluorescent Proteins (metabolism)
• Neuraminidase (metabolism)
• Rats, Sprague-Dawley
• Sodium-Coupled Vitamin C Transporters (metabolism)