Neurodegenerative diseases (ND) such as: Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis have been linked with environmental exposures to numerous chemicals within a background of genetic risk factors. However, the exact role of environmental agents and the establishment of markers of disease have remained elusive;particularly, early markers that occur prior to disease onset. For ND diseases such as Parkinson's, oxidative stress and mitochondrial dysfunction are known contributing factors and the lipid rich regions of the brain which are critical for neuronal functin are sensitive targets, playing a key role in disease etiology. Localized lipid concentrations offer important information on the functional state and molecular pathobiology of ND. Traditional molecular biology techniques, such as in situ hybridization and immunohistochemistry, are ideally suited for characterization of mRNA and protein abundances while mass spectrometry imaging (MSI) enables identification and spatial localization of individual lipids and metabolites in tissues thereby providing important complementary information. This project is focused on the development of a complementary mass spectrometry-based platform for quantitative imaging of lipids and metabolites in tissues with high spatial resolution and high sensitivity for obtaining molecular markers of the early disease stages at a cellular level. This capability is critical to advancing the molecular level understanding of the effect of environmental chemical exposure on neurodegeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21ES024229-01
Application #
8756251
Study Section
Special Emphasis Panel (ZES1-LWJ-K (R))
Program Officer
Kirshner, Annette G
Project Start
2014-09-11
Project End
2016-08-31
Budget Start
2014-09-11
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$247,233
Indirect Cost
$97,233
Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352
Nguyen, Son N; Sontag, Ryan L; Carson, James P et al. (2018) Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy. J Am Soc Mass Spectrom 29:316-322
Laskin, Julia; Lanekoff, Ingela (2016) Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques. Anal Chem 88:52-73