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

摘要

Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric dis-orders. Developmental lead exposure can cause neurological disorders similar to hyperactivity dis-order, 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 ex-pression 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 ex-pression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.