Microglial disruption in young mice with early chronic lead exposure

Abstract

The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31 μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals.

δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD2) and peptide transporter 2*2 haplotype (hPEPT2*2) differently influence neurobehavior in low-level lead exposed children

“…Working memory is dependent on dentate gyrus (Aimone et al, 2011; Friedman and Goldman-Rakic, 1988; Xavier et al, 1999). Thus, this finding is consistent with the animal literature showing vulnerability of dentate gyrus to higher (Gilbert et al, 1996; Gilbert and Mack, 1998; Gilbert et al, 2005; Gilbert and Lasley, 2007) and lowest levels (Sobin et al, 2013) of lead exposure. Dentate gyrus is one of only three brain regions that supports neurogenesis throughout the lifespan and studies have also shown how higher levels of lead exposure alter neurogenesis (Gilbert et al, 2005).…”

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

“…Perhaps consistent with these findings, memory impairments have been found in children with BLLs similar to those of the low-dose mice in this study (<5 μg dl −1 ) (e.g., Min et al , 2007; Surkan et al , 2007). In addition, in brain studies of pre-adolescent C57BL/6J mice exposed to chronic low-level lead, abnormalities in hippocampus/dentate gyrus were identified (Sobin et al , 2013). The results of these studies should be interpreted cautiously.…”

Ginger extract modulates Pb-induced hepatic oxidative stress and expression of antioxidant gene transcripts in rat liver

“…Pb-induced oxidative stress or disruption of the pro-oxidant/antioxidant balance in blood and soft tissues is postulated to be the major mechanism of various tissue injuries (Ashry et al, 2010;Flora et al, 2003). Chronic exposure to Pb results in its accumulation, mainly in the liver, kidneys, and brain, as well as in other organs and tissues, where it causes many metabolic and histological changes, membrane damage, altered gene expression, and apoptosis (Kojima et al, 2002;Quintanilla-Vega et al, 2000;Sobin et al, 2013;Wang et al, 2013b). It causes oxidative stress by inducing the generation of reactive oxygen species (ROS), increasing the levels of lipid peroxidation (LPO) and thiobarbituric acid-reactive substances (TBARs), and inhibiting the activity of many antioxidant biomolecules (AlcarazContreras et al, 2011;Ashry et al, 2010).…”