|Abstract Title:||Developmental Neurotoxicity Effects of Low doses of MeHg in Zebrafish Embryo and Human Neural Stem Cell Models|
|Presenter Name:||Ana Isabel Cañas Portilla|
|Company/Institution:||Centro Nacional de Sanidad Ambiental|
|Session:||Progress in understanding Hg and human health impacts|
|Co-Authors:||Ana Isabel Cañas Portilla|
Abstract Information :
The organic form of mercury (MeHg) is a highly toxic compound and neurotoxicity has been observed even at very low levels. However, both epidemiological and in vitro/in vivo studies show dissimilar results regarding specific effects, dose-responses, and mechanisms of action. Therefore, to further investigate effects of low MeHg doses on developmental neurotoxicity, we have examined effects of nanomolar MeHg concentrations (10, 30, 70 and 100 nM) on the long-term propagated neural stem cell line hNS1 (self-renewing and multipotent) and the zebrafish embryo (ZFE) model. Effects of MeHg on cell death and proliferation of differentiating hNS1 cells was evaluated by Caspase 3, Ki67, vimentin, Sox 2 and Sox10 RNA and protein levels. Effects of MeHg in cell fate specification was evaluated by ?-tubulin III (neuronal marker), and GFAP (astrocyte marker) protein and RNA expression. Effects on ZFE were evaluated for early motor-response by the tail-coiling assay at 24 h post fertilization (hpf), and for more complex behaviors at 120 hpf through the visual motor response test during light/dark cycles, anxiety in response to visual and auditory stimuli, startle response, and habituation assays. In addition, effects on sensory organ development (eye and otolith) were evaluated. Our results show that MeHg induces apoptotic death, cell proliferation and increases differentiation to glial phenotype without changes on neural differentiation in a dose-dependent manner, being cytotoxic from 100nM. Developmental neurotoxicity in ZFE was evidenced by changes in behavioral patterns and sensory organ development. In particular, locomotion activity and anxiety showed greater effects at low-intermediate doses but habituation to startle stimuli and sensory organ size were largely dose-dependent. However, specific effect dose-dependence was determined by endpoint studied, stimuli type (visual or auditory) and developmental stage. Our study adds to growing evidence for MeHg peculiarities as a neurotoxicant, especially when organisms are exposed to very low doses.