title: Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.
abstract: 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.
authors.affiliation: Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Paradells
authors.affiliation: Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.
authors.forename: Brenda
authors.initials: B
authors.lastname: Rocamonde
authors.affiliation: Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Llinares
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, 46980, Paterna, Valencia, CIBERNED, Spain.|Unidad mixta de Esclerosis múltiple y neurorregeneración, IIS Hospital La Fe-UVEG, 46013, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Herranz-Pérez
authors.affiliation: Departamento de Microbiología y Ecología, Universitat de València, Burjassot, Spain.
authors.forename: Misericordia
authors.initials: M
authors.lastname: Jimenez
authors.affiliation: Laboratorio de Neurobiología Comparada, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, 46980, Paterna, Valencia, CIBERNED, Spain.|Unidad mixta de Esclerosis múltiple y neurorregeneración, IIS Hospital La Fe-UVEG, 46013, Valencia, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.affiliation: Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.|Instituto de Ciencias Biomédicas Universidad CEU Cardenal Herrera, Avda. Seminario, 46113, Moncada, Valencia, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Zipancic
authors.affiliation: Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.|Instituto de Ciencias Biomédicas Universidad CEU Cardenal Herrera, Avda. Seminario, 46113, Moncada, Valencia, Spain.
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Soria
authors.affiliation: Facultad Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario, 46113, Moncada, Valencia, Spain.|Instituto de Ciencias Biomédicas Universidad CEU Cardenal Herrera, Avda. Seminario, 46113, Moncada, Valencia, Spain.
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Garcia-Esparza
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020547:Lateral Ventricles / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009183:Mycotoxins / Q000633:toxicity*; D058953:Neural Stem Cells / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009793:Ochratoxins / Q000633:toxicity*
chemical_list: D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A
keywords: Ochratoxin A; cell differentiation; cell proliferation; cell viability; mycotoxin; subventricular zone