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Toxicological Sciences 63, 74-81 (2001)
Copyright © 2001 by the Society of Toxicology

NEUROTOXICOLOGY

Methylmercury-Induced Decrement in Neuronal Migration May Involve Cytokine-Dependent Mechanisms: A Novel Method to Assess Neuronal Movement in Vitro

J. B. Sass*,1,2, D. T. Haselow{dagger} and E. K. Silbergeld*

* Program in Human Health and the Environment and {dagger} Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland 21201

A major toxic effect associated with methylmercury (MeHg) exposure in developing humans is damage to the nervous system, which involves inhibition of cell migration, particularly in the cerebellum. The mechanisms by which MeHg impairs neural migration are not fully known, especially at low doses. In this paper we report on a novel method for observing and quantitating the movement of individual cells in primary cultures of murine neonatal cerebellar cells, which offers an opportunity to assess the role of endogenous and exogenous factors on neural migration. We have used this system to test the hypothesis that treatment with methylmercury would inhibit movement of granule cell neurons, possibly via a cytokine-mediated mechanism. We demonstrate that LPS (50 ng/ml) increases movement of neurons, concomitant with increased levels of TNF-{alpha} and IL-6 secreted protein, and IL-1{alpha} mRNA. Treatment with LPS did not increase the number of neurons that moved, but, of the cells that did move, exposure to LPS significantly increased the total distances moved. Treatment with methylmercury (0.1 µM) decreased the number of moving cells and inhibited overall distance traveled by granule cells.

Key Words: methylmercury; neurodevelopment; cytokine; migration; cerebellum; cell signaling.


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