CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCEMethylmercury inhibits differentiation of rat neural stem cells via Notch signallingTamm, Christoffera; Duckworth, Joshua K.b; Hermanson, Olab; Ceccatelli, SandraaAuthor Information aDivision of Toxicology and Neurotoxicology, Institute of Environmental Medicine bDepartment of Neuroscience, Center of Excellence in Developmental Biology (CEDB/DBRM), Karolinska Institutet, Stockholm, Sweden Correspondence to Sandra Ceccatelli, Karolinska Institutet, Nobelsvag 13, SE-171 77 Stockholm, Sweden Tel: +46 8 52487586; fax: +46 8 329041; e-mail: firstname.lastname@example.org Received 27 November 2007; accepted 2 December 2007 NeuroReport: February 12th, 2008 - Volume 19 - Issue 3 - p 339-343 doi: 10.1097/WNR.0b013e3282f50ca4 Buy Metrics Abstract The Notch receptor is essential for neural stem cell (NSC) characteristics. Relatively high concentrations (micromolar) of methylmercury (MeHg) activate Notch signalling in Drosophila cell lines; however, exposure of MeHg at such concentrations is rare, and the implications for mammalian cells are unclear. We have shown that MeHg at a nanomolar range inhibits neuronal differentiation of rodent embryonic NSCs. Here we show that low MeHg levels (2.5–10 nM) activated Notch signalling in NSCs, as assessed by the increased activity in a specific Notch-reporter assay and by the increased cleavage of the Notch intracellular domain. Importantly, pretreatment with Notch cleavage inhibitor reversed the MeHg-induced repression of neuronal differentiation, suggesting that Notch activation is involved in the inhibition of NSC differentiation by environmentally relevant levels of MeHg. © 2008 Lippincott Williams & Wilkins, Inc.