Paradells Sara, Rocamonde Brenda, Llinares Cristina, Herranz-Pérez Vicente, Jimenez Misericordia, Garcia-Verdugo Jose Manuel, Zipancic Ivan, Soria Jose Miguel, Garcia-Esparza Ma Angeles
Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.
Laboratorio de Neurobiología Comparada, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, 46980, Paterna, Valencia, CIBERNED, Spain.
J Appl Toxicol. 2015 Jul;35(7):737-51. doi: 10.1002/jat.3061. Epub 2014 Sep 25.
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.
赭曲霉毒素A（OTA）是一种作为曲霉属和青霉属真菌次生代谢产物而被发现的霉菌毒素，是食品和动物饲料中的常见污染物。这种霉菌毒素已被描述为具有致畸性、致癌性、基因毒性、免疫毒性，并且已被证明是一种强效神经毒素。其他作者此前曾报道过OTA对中枢神经系统不同结构以及一些神经源性区域的影响。然而，尚未评估OTA暴露对脑室下区（SVZ）的影响。为了阐明OTA是否会影响小鼠SVZ的神经前体细胞，我们在体外和体内研究了OTA暴露对SVZ以及从这个神经源性微环境中获取的神经前体细胞的影响。在这项工作中，我们证明了OTA暴露对从SVZ培养的神经干细胞的增殖、分化和消耗具有累积效应。此外，我们通过免疫组织化学和电子显微镜在体内证实了这些结果。结果，我们发现增殖过程发生了显著改变，这表现为5-溴-2-脱氧尿苷阳性细胞和神经胶质细胞数量减少，以及SVZ中神经母细胞数量显著减少。总之，在本研究中我们证明了OTA如何通过以剂量依赖方式影响细胞活力、增殖和分化，对发育中的和成年的SVZ构成威胁。
