The effects of lead (Pb) on the developing nervous system are well documented and the removal of Pb from gasoline has greatly diminished the risk from environmental exposure to Pb. However, exposure to Pb remains a serious occupational concern. Many workers who are currently employed in industries such as mining, construction, and manufacturing are faced with this occupational hazard everyday. While adult exposure to Pb can damage various organs in the body, new data suggests that prior exposure to Pb may intensify these responses. These data arise primarily from epidemiological observations that have shown that some adult chronic non-communicable diseases are not only influenced by genetic and life-style factors but by environmental factors acting in the perinatal and infant phases of life. Recently, Basha et al., (2005) reported that developmental exposure of rats to the heavy metal Pb resulted in a delayed over-expression (20 months later) of the Amyloid Precursor Protein (APP) and its amyloidogenic AB product. APP and AB are integral components of amyloid plaques, the key pathological feature of Alzheimer's disease (AD). Additionally, developmental exposure to Pb resulted in an accumulation of oxidative DNA damage in old age, a process associated with many adult diseases (Bolin et al., 2006). These delayed effects indicate that a critical developmental window exists for chemical exposure that predetermines future susceptibility to disease and suggests that workers with a past history of exposure may be at greater risk of developing certain diseases. To address this issue, we will use animal models to examine the consequences to biomarkers of neurodegenerative diseases in the brains and blood of animals who were developmentally-exposed to Pb and which undergo repeated exposure as adults. We further would like to examine the mechanisms associated with sensitization of animals to disease by early life exposure and how such processes respond in the event of re-exposure during adulthood.

Public Health Relevance

An estimated 10% of Americans over the age of 65 and half of those over age 85 have AD. The number of people suffering from this neurodegenerative disease is expected to increase exponentially in the coming decades due to an increasing lifespan and an aging baby-boomer generation. Both sporadic and inherited forms of AD can be impacted by lifestyle and work environment. Published work has suggested a potential link between AD and exposure to lead (Pb). Therefore, It is crucial to investigate the role of environmental and occupational exposure and to develop biomarkers that can guide prevention and therapeutic interventions. Since the brain serves as the only source of conclusive biomarkers for AD, it is crucial to identify reliable biomarkers in accessible tissues such as blood that could be utilized for early detection of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015867-04
Application #
8197587
Study Section
Special Emphasis Panel (ZRG1-CND-E (90))
Program Officer
Kirshner, Annette G
Project Start
2009-02-03
Project End
2013-11-30
Budget Start
2011-12-05
Budget End
2013-11-30
Support Year
4
Fiscal Year
2012
Total Cost
$313,448
Indirect Cost
$92,925
Name
University of Rhode Island
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
144017188
City
Kingston
State
RI
Country
United States
Zip Code
02881
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