Adult hippocampal neural stem/progenitor cells in vitro are vulnerable to the mycotoxin ochratoxin-A.
The common mycotoxin ochratoxin-A (OTA) accumulates in brain, causes oxidative stress, and elicits a DNA repair response that varies across brain regions and neuronal populations. Neural stem/progenitor cells (NSCs) prepared from hippocampus of adult mouse brain were tested for their vulnerability to the toxin in vitro. The following measurements were made in NSC cell cultures in both proliferation and differentiation media: (1) viability (trypan blue exclusion), (2) proliferative activity ([(3)H]-thymidine uptake), (3) the DNA repair response (oxyguanosine glycosylase activity), and (4) antioxidative response (superoxide dismutase). Cells that had proliferated to 90-100% confluency in the presence of epidermal growth factor and basic fibroblast growth factor were induced to differentiate by removal of the growth factors. OTA, added to the cultures in concentrations of 0.01-100 microg/ml, caused a dose- and time-dependent (6-72 h) decrease in viability of both proliferating and differentiating NSC. Proliferating NSC exhibited a greater vulnerability to the toxin than differentiated neurons despite robust DNA repair and antioxidative responses. Preconditioning of NSC with a 12-h incubation with the pro-oxidant diethyl maleate increased DNA repair activity and, subsequently, provided a moderate degree of neuroprotection. Overall, these results lead to speculation that OTA exposure may contribute to impaired hippocampal neurogenesis in vivo, resulting in depression and memory deficits, conditions reported to be linked to mycotoxin exposure in humans.
Sava
Vasyl
V
Department of Neurology, University of South Florida, James Haley VA Hospital, Tampa, Florida 33612, USA.
Velasquez
Adriana
A
Song
Shijie
S
Sanchez-Ramos
Juan
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008298:Maleates / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D009793:Ochratoxins / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity; D013234:Stem Cells / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D000975:Antioxidants; D008298:Maleates; D009793:Ochratoxins; D016877:Oxidants; C025589:ochratoxin A; D013482:Superoxide Dismutase; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C014476:diethyl maleate; D005978:Glutathione; D013936:Thymidine