Low level lead exposure and inflammatory markers in the brains of C57BL/6J mice

Background and Significance: Prior studies have indicated that early chronic low-level lead exposure may be associated with adverse effects on motor and cognitive functions. The mechanisms by which low-level lead affects brain function are unknown. Objectives: The current study aimed to (1) determine whether early chronic low-level lead exposure altered the expression of pro- or ant-inflammatory cytokines and markers of oxidative stress in mouse brain studied at two ages, pre-adolescence (PND 28) and early adulthood (PND 40); and (2) in the same pre-adolescent and early adulthood mice, compare and contrast the levels of pro- or ant-inflammatory markers in three brain regions including anterior cerebrum, posterior cerebrum and cerebellum. Hypothesis: We hypothesized that early chronic exposure to low-level lead triggers abnormal expression of pro- or ant-inflammatory markers consistent with an inflammatory response and oxidative stress in younger and older mice; and that posterior cerebrum would be more susceptible to the effects of chronic low-level lead than anterior cerebrum and cerebellum. Methods: Two studies were conducted one in 28 day and one in 40 day old C57BL/6J mice. For each study, mice were assigned to one of three experimental groups including a control group (no lead exposure), a low dose group (exposed to 40 ppm lead acetate), and a high dose group (exposed to 230 ppm lead acetate). Mice were exposed to lead acetate (99.4% pure) via dams’ drinking water from birth until weaning. The gene expression levels of four pro-inflammatory markers (TNF-?, IFN-?, IL-6, iNOS), two immune-suppressive markers (IL-10 and Hmox-1) and an oxidative stress indicator GPR-78 were measured in homogenized brain sections from anterior cerebrum, posterior cerebrum and cerebellum using qRT-PCR. These markers were selected because they have roles in brain development and inflammatory responses (Bauer, Kerr, & Patterson, 2007; Ahamed & Siddiqui, 2007; Anthony & Campbell, 2002; Bokara, et al., 2008; Cabell, et al., 2004; Deverman & Patterson, 2009; Gastaldello Moreira, de Magalhaes Rosa, Moraes Barros, Vassilieff, & Vassillieff, 2001) Results: There were no statistically significant differences observed in pre-adolescent mice. Young adult lead-exposed mice had significant differences in genetic expression of TNF-?, Hmox-1, and GRP-78. Lowest level lead exposure caused a statistically significant increase in genetic expression of TNF-? and Hmox-1 in the low dose group when compared to the control group. Conclusions: A mixed inflammatory response is activated due to chronic exposure to low-level lead in young adult mice. Additional studies are needed to further define the role of chronic low level lead exposure in interfering with normal brain function