Increased hippocampal Disrupted-In-Schizophrenia 1 expression in mice exposed prenatally to lead.

Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric disorders. Developmental lead exposure can cause neurological disorders similar to hyperactivity disorder, dyslexia and schizophrenia. In the present study, we examined the impact of developmental lead exposure, administered in vitro and in vivo, on hippocampal Disrupted-In- Schizophrenia 1 expression. Our results show that in cultured hippocampal neurons, in vitro exposure to 0.1-10 µM lead, inhibited neurite growth and increased Disrupted-In-Schizophrenia 1 mRNA and protein expression dose-dependently. In addition, blood lead levels in mice were increased with increasing mouse maternal lead (0.01-1 mM) exposure. Hippocampal neurons from these mice showed a concomitant increase in Disrupted-In-Schizophrenia 1 mRNA and protein expression. Overall our findings suggest that in vivo and in vitro lead exposure increases Disrupted-In-Schizophrenia 1 expression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.