Szentgyörgyi Viktória, Tagscherer-Micska Brigitta, Rátkai Anikó, Schlett Katalin, Bencsik Norbert, Tárnok Krisztián
Department of Physiology and Neurobiology, Institute of Biology, Eötvös Loránd University, H-1053 Budapest, Hungary.
Toxins (Basel). 2025 Jul 25;17(8):368. doi: 10.3390/toxins17080368.
Fumonisin B1, deoxynivalenol (DON), and zearalenone (ZEA) are toxic secondary metabolites produced by molds. These mycotoxins are common food and feed pollutants and represent a risk to human and animal health. Although the mycotoxins produced by this genus can cross the blood-brain barrier in many species, their effect on neuronal function remains unclear. We investigated the cell viability effects of these toxins on specified neural cell types, including mouse primary neuronal, astroglial, and mixed-cell cultures 24 or 48 h after mycotoxin administration. DON decreased cell viability in a dose-dependent manner, independent of the culture type. Fumonisin B1 was toxic in pure neuronal cultures only at high doses, but toxicity was attenuated in mixed and pure astroglial cultures. ZEA had significant effects on all culture types in 10 nM by increasing cell viability and network activity, as revealed by multi-electrode array measurements. Since ZEA is a mycoestrogen, we analyzed the effects of ZEA on the expression of estrogen receptor isotypes ERα and ERβ and the mitochondrial voltage-dependent anion channel via qRT-PCR. In neuronal and mixed cultures, ZEA administration decreased ERα expression, while in astroglial cultures, it induced the opposite effect. Thus, our results emphasize that mycotoxins act in a cell-specific manner.
伏马菌素B1、脱氧雪腐镰刀菌烯醇（DON）和玉米赤霉烯酮（ZEA）是霉菌产生的有毒次生代谢产物。这些霉菌毒素是常见的食品和饲料污染物，对人类和动物健康构成风险。尽管该属产生的霉菌毒素在许多物种中可穿过血脑屏障，但其对神经元功能的影响仍不清楚。我们在给予霉菌毒素24或48小时后，研究了这些毒素对特定神经细胞类型的细胞活力影响，包括小鼠原代神经元、星形胶质细胞和混合细胞培养物。DON以剂量依赖方式降低细胞活力，与培养类型无关。伏马菌素B1仅在高剂量时对纯神经元培养物有毒，但在混合和纯星形胶质细胞培养物中毒性减弱。如多电极阵列测量所示，10 nM的ZEA通过增加细胞活力和网络活性对所有培养类型都有显著影响。由于ZEA是一种霉菌雌激素，我们通过定量逆转录聚合酶链反应分析了ZEA对雌激素受体亚型ERα和ERβ以及线粒体电压依赖性阴离子通道表达的影响。在神经元和混合培养物中，给予ZEA会降低ERα表达，而在星形胶质细胞培养物中则产生相反效果。因此，我们的结果强调霉菌毒素以细胞特异性方式起作用。
