Developmental synapse pathology by exposure to herbicide glufosinate ammonium

Abstract

Epidemiological studies suggest that maternal pesticide exposure is associated with increased risks of developmental disorders in offspring. Although synaptic signaling is crucial for the formation and maturation of neural circuits, the effects of exposure to pesticide on neuronal synapse are still unclear. Thus, in this study, we examined whether prenatal glufosinate ammonium (GLA) exposure affects the regulation of synapse formation. During gestation period, GLA or saline were administered to pregnant mice by intranasal route. Primary cultured cortical neurons from the offspring brain were prepared for synapse formation assay and microarray analysis of gene expression. As a result of measuring the ability to induce differentiation into presynaptic terminals, neurons from GLA-treated group showed a significant decrease in the amount of presynaptic terminals compared to those from saline-administered control group. Consistent with this, microarray analysis along the stage of neuronal development resulted in the decrease of genes related to nervous system development in neurons from GLA-treated group. Furthermore, comparison of gene expression between before and after synaptic induction revealed that induction of several activity-regulated genes was suppressed in the GLA-exposed group.Our results suggested that prenatal GLA exposure affects at least a part of presynaptic differentiation, resulting in alterations in neural network construction. We are continuing to analyze the molecular mechanisms underlying this synaptic pathology.