Adult Hippocampal Neural Stem/Progenitor Cells In Vitro Are Vulnerable to the Mycotoxin Ochratoxin-A Export

@article{citeulike:4069361, abstract = {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 ([3H]-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 {micro}g/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. 10.1093/toxsci/kfm093}, author = {Sava, Vasyl and Velasquez, Adriana and Song, Shijie and Sanchez-Ramos, Juan}, citeulike-article-id = {4069361}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/toxsci/kfm093}, citeulike-linkout-1 = {http://toxsci.oxfordjournals.org/cgi/content/abstract/98/1/187}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17449898}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17449898}, day = {1}, doi = {10.1093/toxsci/kfm093}, journal = {Toxicol. Sci.}, keywords = {achratoxin-a, hippocampus, mycotoxins}, month = {July}, number = {1}, pages = {187--197}, posted-at = {2009-02-19 02:34:06}, priority = {3}, title = {Adult Hippocampal Neural Stem/Progenitor Cells In Vitro Are Vulnerable to the Mycotoxin Ochratoxin-A}, url = {http://dx.doi.org/10.1093/toxsci/kfm093}, volume = {98}, year = {2007} }

TY - JOUR ID - citeulike:4069361 L3 - citeulike-article-id:4069361 N2 - 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 ([3H]-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 {micro}g/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. 10.1093/toxsci/kfm093 IS - 1 JF - Toxicol. Sci. EP - 197 TI - Adult Hippocampal Neural Stem/Progenitor Cells In Vitro Are Vulnerable to the Mycotoxin Ochratoxin-A VL - 98 SP - 187 KW - achratoxin-a KW - hippocampus KW - mycotoxins AU - Sava, Vasyl AU - Velasquez, Adriana AU - Song, Shijie AU - Sanchez-Ramos, Juan PY - 2007/07/01/ UR - http://dx.doi.org/10.1093/toxsci/kfm093 ER -