Abstract

Vitamin C is an essential molecule in all living systems; however, humans are among the few species that are not able to synthetize it and must acquire from the diet. The role of this nutrient in human health and disease is still an important matter of debate, since most pathological processes are linked to oxidative stress and vitamin C, as a reducing agent, should be key in disease prevention, including cancer and neurodegenerative disorders. Still, there is not a clear connection between vitamin C consumption and neurodegeneration. To determine which might be the links between AD and vitamin C uptake machinery we aimed to detect how Aβ exposure on neuronal tissue and cells changes vitamin C uptake capacities by analyzing Na+/Vitamin C cotransporter. In a firsts approach, we test SVCT expression in a murine model of AD, J20 mice. Interestingly, we found increased expression of a mitochondrial form of SVCT2 in this model in comparison to age-match normal mice with the same genetic background. Later, to detect if whether this over-expression was related to Aβ increase, we exposed hippocampal and cortical primary cell culture from normal mice to Aβ oligomers. However, increasing amounts of Aβ oligomers did not alter SVCT2 expression in the mitochondria. In fact, most of SVCT2 was not located within the mitochondria. Surprisingly, SVCT2 expression was not only detected in the cytosol, but also it was increased after treatment with oligomeric Aβ exposure, as demonstrated by immunofluorescence and WB. Then, in order to know if human cells exhibit some differences with mice, we performed the same analysis in neuronal derived human cells SHSY-5Y, which showed mitochondrial localization of SVCT2. We concluded that even though exposure to amyloids are associated with an increase in SVCT2, this increased expression is not related to the mitochondria. Further analysis should be performed to determine the localization of SVCT2 in neuronal mice models.