Project 2, which will be new to the UW SBRP, is an epidemiologic investigation of the roles of metals as determinants of the risk, severity, and progression of parkinsonism (PS) among professional welders. Previous epidemiologic and experimental research has demonstrated very plausible links between manganese (Mn) and other metals, individually and in combination, and PS. The study population includes 875 Wisconsin shipyard welders (775 actively employed, 100 retired) and 200 non-exposed shipyard workers with no welding exposure history previously enrolled in an ongoing NEIHS-funded R01 (ES013743;PI: B. Racette;Co-investigators: H. Checkoway, N. Seixas). The new features of this proposed study will be the refinement of exposure assessment to generate quantitative metal-specific levels, and repeated neurological examinations of longitudinal change of PS-related motor function. The scientific objectives of the project are to: 1) estimate dose-response relations between Mn and other metal exposures and PS risk and severity;2) test the hypothesis that these metal exposures are associated with PS progression;3) determine the predictive relations of PS proteomic biomarkers, characterized in Project 3 (Dr. Zhang), with PS risk, severity, and progression;4) test dose-response relations for Mn and other metals with PS proteomic biomarker profiles as indicators of preclinical disease. To achieve these objects, we will perform repeated standardized neurological exams of motor function (Unified Parkinson's Disease Rating Scale Motor Subsection 3 [UPDRS3]) 3 years after enrollment exams for as many study subjects as can be enrolled (~75%). Addionally, in collaboration with Project 3, we will collect plasma samples for assays of proteomics that have been validated as strongly associated with PS for a sample of 150 subjects selected according to baseline UPDRS3 ('normal', borderline PS, probable/definite PS). Data on potentially important confounding factors, especially cigarette smoking and pesticide exposure, will be obtained by questionnaire. This project has great potential to quantify the extent of neurological effects of metals, which are widespread environmental contaminants, and thus could contribute to disease prevention strategies.
Manganese (Mn) and other metals are widespread environmental contaminants, and have been linked with adverse neurological effects, especially parkinsonism (PS). This study will investigate epidemiologic associations between these metals and risk, severity, and progression of PS among professional welders. The findings have great potential to generate important new knowledge for disease prevention.
|Meador, James P; Yeh, Andrew; Gallagher, Evan P (2017) Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations. Environ Pollut 230:1018-1029|
|Chang, Yu-Chi; Cole, Toby B; Costa, Lucio G (2017) Behavioral Phenotyping for Autism Spectrum Disorders in Mice. Curr Protoc Toxicol 72:11.22.1-11.22.21|
|Roqué, Pamela J; Costa, Lucio G (2017) Co-Culture of Neurons and Microglia. Curr Protoc Toxicol 74:11.24.1-11.24.17|
|Wang, Hao; Engstrom, Anna K; Xia, Zhengui (2017) Cadmium impairs the survival and proliferation of cultured adult subventricular neural stem cells through activation of the JNK and p38 MAP kinases. Toxicology 380:30-37|
|Yeh, Andrew; Marcinek, David J; Meador, James P et al. (2017) Effect of contaminants of emerging concern on liver mitochondrial function in Chinook salmon. Aquat Toxicol 190:21-31|
|Mills, Margaret G; Gallagher, Evan P (2017) A targeted gene expression platform allows for rapid analysis of chemical-induced antioxidant mRNA expression in zebrafish larvae. PLoS One 12:e0171025|
|Costa, Lucio G; Cole, Toby B; Coburn, Jacki et al. (2017) Neurotoxicity of traffic-related air pollution. Neurotoxicology 59:133-139|
|Costa, Lucio G; Cole, Toby B; Garrick, Jacqueline M et al. (2017) Metals and Paraoxonases. Adv Neurobiol 18:85-111|
|Al-Lozi, Amal; Nielsen, Susan Searles; Hershey, Tamara et al. (2017) Cognitive control dysfunction in workers exposed to manganese-containing welding fume. Am J Ind Med 60:181-188|
|Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2017) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology :|
Showing the most recent 10 out of 443 publications