Date of Award

2017-01-01

Degree Name

Doctor of Philosophy

Department

Psychology

Advisor(s)

Christina Sobin

Abstract

Chronic low-level lead exposure reduces memory in children however the brain mechanisms mediating these effects are not known. In previous studies we showed that early lead exposure reduced olfactory memory and exploratory behavior in young mice, and reduced microglia cell density in hippocampus/dentate gyrus. The present studies aimed to identify additional behavioral tests that were sensitive to early low-level lead exposure in young mice; and to examine whether microglia upregulated factors known to promote cell migration. Seventy-two C57BL/6J male mice were exposed to 0 ppm (controls), 30 ppm (low-dose), or 430 ppm (high-dose) of lead acetate via dams' milk from PND 0 to 28. Behavioral studies and a microglial cell study were conducted. For behavioral studies, mice were tested for developmental milestones (body weight, eye-opening, and righting reflex), muscle strength (inverted screen test), exploratory activity and/or anxiety (open field), and olfactory memory (odor habituation/dishabituation task). For microglia studies, levels of major histocompatibility complex (MHC) II and C-C chemokine receptor 7 (CCR7) in hippocampal and brain microglia were quantified with fluorescence activated cell sorting analyses (FACS). For behavioral studies, it was found that chronic low-level lead exposure increased body weight and decreased exploratory activity. For microglial cell studies, it was found that chronic low-level lead exposure decreased MHC II and CCR7 surface expression in hippocampal microglia. Exploratory analyses revealed additional effects in macrophages and immune cells. These results suggested that chronic low-level lead exposure disrupts exploratory behavior, alters body weight, and disrupts the early neuroimmune system in young mice. Future studies should examine whether alterations in memory and exploratory activity are mediated either by trafficking of microglial cells outside of brain and/or disruption of MHC II and CCR7.

Language

en

Provenance

Received from ProQuest

File Size

250 pages

File Format

application/pdf

Rights Holder

Mayra Gisel Flores-Montoya

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