The effects of developmental sub-chronic low-level lead exposure on microglia and a test of possible mitigation by apigenin in C57BL/6J young mice.

Abstract

Developmental chronic low-level lead (Pb) exposure disrupts central nervous system function and diminishes neurocognition. Microglial cell activation might contribute to these deficits. The present study evaluated the effects of developmental sub-chronic low-level lead exposure on microglial cells and the possible effectiveness of a natural anti-inflammatory intervention with apigenin to mitigate these effects. From PND 0 to 28, 87 C57BL/6 J mice were exposed to one of six treatment conditions: 0 ppm Pb; 30 ppm Pb; 430 ppm Pb; 30 ppm Pb + 400 ppm apigenin; 430 ppm Pb + 400 ppm apigenin; or 400 ppm apigenin, via dams' drinking water. Following sacrifice, brain tissue was harvested and microglial cells were labeled via immunohistochemistry and counted within the dentate gyrus (DG) using unbiased stereology methods. It was hypothesized that developmental sub-chronic low-level lead exposure would increase microglial cell numbers within the DG and that apigenin treatment may mitigate these effects. A significant effect of treatment group was found and post-hoc analyses revealed that Pb-exposure generated an increased number of microglial cells as compared to controls. Interestingly, the 30 ppm Pb with apigenin treatment group did not generate microglial cell numbers different from the control group unexposed to Pb. These results suggested that developmental sub-chronic low-level lead exposure increased microglial cell activation within the DG and that, at low-levels of Pb exposure, apigenin treatment may mitigate these effects. These results provided the groundwork for studies that could identify an effective intervention to alleviate the effects of developmental chronic low-level lead exposure in child neurocognition.