Effect of developmental lead exposure on neurogenesis and cortical neuronal morphology in Wistar rats

Abstract

Lead (Pb) is a neurotoxic heavy metal that largely affects the developing nervous system. The present study examined the temporal effect of perinatal Pb exposure on neurogenesis and cortical neuronal morphology. Wistar pregnant rats were exposed to 0.5% lead acetate throughout pregnancy and to postnatal day (PD) 28. Offspring were grouped as gestational day (GD) 18 and 21 and PD 7, 14, 21, and 28 in both control and experimental groups. Brain sections were processed for immunohistological staining with anti-proliferating cell nuclear antigen (PCNA) or glial fibrillary acidic protein (GFAP). Brains from 14, 21, and 28 PDs pups were processed for Golgi–Cox stain. Pb exposure significantly increased PCNA-positive nuclei in the ventricular and subventricular zones of the lateral ventricle at 18 and 21 GDs. Postnatally, the Pb-treated groups showed a significant decrease in PCNA-positivity and neuron density compared to control. This reduction was associated with an increase in damaged or apoptotic cell profiles in the experimental groups. At PD 21, there was a significant increase in GFAP immunoreactivity in Pb-exposed groups compared with control. Furthermore, the total apical and basal dendritic length of pyramidal neurons in layer 2–3 of the Golgi–Cox stained sensorimotor cortex was comparable in both control and Pb-exposed groups. Spine density per 10 µm was significantly increased at PD 14 and 21 on the apical dendrites but not basal dendrites of Pb-treated groups. In conclusion, developmental Pb exposure in rats induces a toxic effect on neurogenesis and on cortical neurons, which may be related to cognitive disabilities observed in children exposed to lead.