Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain

• Published in: Journal of applied toxicology 2015-07, Vol.35 (7), p.737-751
• Main Authors: Paradells, Sara, Rocamonde, Brenda, Llinares, Cristina, Herranz-Pérez, Vicente, Jimenez, Misericordia, Garcia-Verdugo, Jose Manuel, Zipancic, Ivan, Soria, Jose Miguel, Garcia-Esparza, Ma. Angeles
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Brain; cell differentiation; Cell Differentiation - drug effects; cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; cell viability; Cells, Cultured; Dose-Response Relationship, Drug; Food contamination & poisoning; Lateral Ventricles - drug effects; Lateral Ventricles - pathology; Lateral Ventricles - ultrastructure; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron; mycotoxin; Mycotoxins - toxicity; Neural Stem Cells - drug effects; Neuroglia - drug effects; Neurotoxicity; Ochratoxin A; Ochratoxins - toxicity; Rodents; subventricular zone
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3061

Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5‐bromo‐2‐deoxyuridine‐positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose‐dependent manner. Copyright © 2014 John Wiley & Sons, Ltd. Ochratoxin A (OTA) is a common contaminant in food and feedstuffs. In the present study we investigated, in vitro and in vivo, the effect of OTA exposure on the subventricular zone (SVZ) and on neural precursors obtained from this neurogenic niche in the adult brain. We demonstrate how OTA could be a threat to SVZ precursors and adult SVZ neurogenic niche through its impact in cell viability, proliferation and differentiation in a dose‐dependent manner.