Pathological analysis of nervous system tissues remains the standard for defining neurodegenerativediseases, monitoring their progression, and evaluating the effects of experimental or therapeuticmanipulations. Imaging is critical for performing neuropathological analyses and has emerged as a powerfulindependent approach for investigating dynamic physiological and pathophysiological processes. Theproposed program project will take maximal advantage of these valuable approaches. Accurate pathologicalanalyses requires the expert handling and preparation of cells and tissues for study and can require the skillsof a trained neuropathologist to interpret the findings. Effective application of imaging approaches requireswell-maintained state-of-the-art equipment, ample opportunities for education and training, and theavailability of expert consultancy. The main goals of this core are to provide the resources to project leadersof this program and enable them to address their research questions efficiently and conclusively withimaging and neuropathology approaches.To accomplish these goals, the Microscopy and Neuropathology Core proposes:
Aim 1, to assistprogram members with the fixation and processing of brain tissues and neural cultures;
Aim 2, to performroutine histological staining of cells and tissues and support immunostaining required for neuropathologicalstudies;
Aim 3, to assist and train program members in the microscopic imaging and digital documentation oftheir imaging data;
Aim 4, to provide assistance with quantitative image analysis of morphological andimmunolabeling data;
and Aim 5, to establish a tissue/section bank and maintain a corresponding onlinedatabase with Core A that is accessible to all projects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG022074-06
Application #
7468580
Study Section
Special Emphasis Panel (ZAG1-ZIJ-3 (J3))
Project Start
2008-06-01
Project End
2013-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
6
Fiscal Year
2008
Total Cost
$220,147
Indirect Cost
Name
J. David Gladstone Institutes
Department
Type
DUNS #
099992430
City
San Francisco
State
CA
Country
United States
Zip Code
94158
Valera, Elvira; Spencer, Brian; Mott, Jennifer et al. (2017) MicroRNA-101 Modulates Autophagy and Oligodendroglial Alpha-Synuclein Accumulation in Multiple System Atrophy. Front Mol Neurosci 10:329
Valera, Elvira; Spencer, Brian; Fields, Jerel A et al. (2017) Combination of alpha-synuclein immunotherapy with anti-inflammatory treatment in a transgenic mouse model of multiple system atrophy. Acta Neuropathol Commun 5:2
Overk, Cassia; Masliah, Eliezer (2017) Perspective on the calcium dyshomeostasis hypothesis in the pathogenesis of selective neuronal degeneration in animal models of Alzheimer's disease. Alzheimers Dement 13:183-185
Spencer, Brian; Desplats, Paula A; Overk, Cassia R et al. (2016) Reducing Endogenous ?-Synuclein Mitigates the Degeneration of Selective Neuronal Populations in an Alzheimer's Disease Transgenic Mouse Model. J Neurosci 36:7971-84
Spencer, Brian; Kim, Changyoun; Gonzalez, Tania et al. (2016) ?-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease. Hum Mol Genet 25:1100-15
Valera, Elvira; Masliah, Eliezer (2016) Therapeutic approaches in Parkinson's disease and related disorders. J Neurochem 139 Suppl 1:346-352
Spencer, Brian; Potkar, Rewati; Metcalf, Jeff et al. (2016) Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease. J Biol Chem 291:1905-20
Valera, E; Monzio Compagnoni, G; Masliah, E (2016) Review: Novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy. Neuropathol Appl Neurobiol 42:95-106
Valera, Elvira; Spencer, Brian; Masliah, Eliezer (2016) Immunotherapeutic Approaches Targeting Amyloid-?, ?-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders. Neurotherapeutics 13:179-89
Valera, Elvira; Masliah, Eliezer (2016) Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord 31:225-34

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