Date of Award

2017-01-01

Degree Name

M.P.H.

Department

Public Health

Advisor(s)

Christina Sobin

Abstract

Background: Lead is a major unresolved child health hazard. Children are uniquely vulnerable to the effects of lead exposure, which include disruption of brain development and brain function. How lead exposure alters brain development and brain function is not currently known. Our laboratory has been developing a mouse model to understand effects of low-level lead exposure in the developing brain. In previous studies, we have shown that early chronic low level lead exposure diminished the number of microglia in the dentate gyrus region of the hippocampus, an area responsible for learning and memory. Building on the results of the previous study, we conducted a study looking at the effects of early chronic low level lead exposure on microglia in the entire hippocampal structure. The current study examined the microglia mean cell body number and distribution of microglia throughout hippocampus in pre-adolescent mice.

Goals of the Study: To determine whether microglia mean cell body number was diminished throughout the entire hippocampal structure of lead exposed mice as compared to controls; whether diminished microglia mean cell body number was unique to dentate gyrus in pre-adolescent mice with early chronic low-level lead exposure; and to examine whether microglial patterns of clustering around neurons differed in lead exposed animals.

Hypotheses: H1): as compared to control animals with no history of lead exposure, in lead exposed animals, microglia mean cell body number is less; H2): as compared to control animals with no history of lead exposure, in lead exposed animals microglia mean cell body number is greater in hippocampal regions that do not include dentate gyrus as compared to hippocampal regions that include dentate gyrus; H3): as compared to control animals with no history of lead exposure, in lead exposed animals hippocampal microglia show greater clustering around neurons

Methods: The study examined the brains of 30 pre-adolescent C57BL/6J mice exposed to one of three possible lead exposure groups including controls (0 ppm), low-dose (30 ppm), and high-dose (330 ppm) animals. Microglia mean cell body number and spatial distribution data were collected using the Stereologer software system (Stereologer Resource Center, Gainesville, FL). Hippocampal volume was also measured. Generalized linear regression models were used to test hypotheses; all models controlled for sex with litter included as a random effect.

Results: Regression analyses showed that microglia mean cell body number was significantly reduced in lead exposed as compared to control animals (main effects for group, F = 44.51, p < .001 and sex, F = 17.14, p < .001); and a significant interaction of group by sex (F = 5.77, p = .01) was found. Parameter estimates and post-hoc tests showed that females in lead-exposed groups had significantly fewer microglia than males. Analyses of microglia mean cell body number in sections of hippocampus with and without dentate gyrus did not differ among groups. Clustering of microglia around neurons did not differ among groups.

Conclusion: The results replicated and expanded on our previous studies and showed that microglia mean cell body number was reduced throughout the hippocampal structure of pre-adolescent lead-exposed animals as compared to controls; and that the distribution of microglia around neurons did not differ in lead exposed animals as compared to controls. These results suggested that hippocampal microglial loss occurs in lead exposed mice before pre-adolescence. Further studies are needed to understand whether early chronic low-level lead exposure destroys microglia during development or somehow causes microglia to be trafficked out of the brain; and at which point in development these changes occur.

Language

en

Provenance

Received from ProQuest

File Size

67 pages

File Format

application/pdf

Rights Holder

Salvador Dominguez

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