Date of Award

2015-01-01

Degree Name

M.P.H.

Department

Public Health

Advisor(s)

Christina Sobin

Abstract

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-α, IFN-γ, 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-α, Hmox-1, and GRP-78. Lowest level lead exposure caused a statistically significant increase in genetic expression of TNF-α 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.

Language

en

Provenance

Received from ProQuest

File Size

61 pages

File Format

application/pdf

Rights Holder

Miguel A. Cervantes

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