Project l of the UCLA Center for the Study of Parkinson's Disease will use quantitative molecular and anatomical techniques to address the central hypothesis of the Center: loss of nigrostriatal neurons, as well as both pharmacological and surgical treatments of Parkinson's disease, alter the molecular and cellular characteristics o neurons of the subthalamic nucleus. Levels and pattern of expression of mRNAs encoding subtypes/subunits of glutamatergic. OABAergic and dopaminergic receptors will be examined in the subthalamic nucleus and its target areas with Polymerase Chain Reaction (PCR) and in situ hybridization histochemistry. This analysis will be extended to genes involved in signal transduction and regulation of these receptors after identification of alterations in the expression of candidate genes with DNA microarray technology in Core C. The following animal models will be generated in Core B and examined in this project: l) rats with nigrostriatal lesions; 2) rats with lesions treated with L-DOPA; 3) rats with lesions and chronic deep brain stimulation of the subthalamic nucleus; 4) rats with lesions and transplants of GABA-producing cells in the subthalamic nucleus. Salient findings will be examined in post-mortem human brain collected as part of CoreB. The data obtained in this project will provide the molecular informatioji necessary for the interpretation of in vitro electrophysioiogical experiments performed in project 2 and in vivo microdialysis and behavioral experiments performed in project 3 on the same animal models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS038367-04
Application #
6618956
Study Section
Special Emphasis Panel (ZNS1)
Project Start
2002-08-01
Project End
2003-07-31
Budget Start
Budget End
Support Year
4
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kusters, Cynthia D J; Paul, Kimberly C; Guella, Ilaria et al. (2018) Dopamine receptors and BDNF-haplotypes predict dyskinesia in Parkinson's disease. Parkinsonism Relat Disord 47:39-44
Chen, Honglei; Ritz, Beate (2018) The Search for Environmental Causes of Parkinson's Disease: Moving Forward. J Parkinsons Dis 8:S9-S17
Richter, Franziska; Subramaniam, Sudhakar R; Magen, Iddo et al. (2017) A Molecular Tweezer Ameliorates Motor Deficits in Mice Overexpressing ?-Synuclein. Neurotherapeutics 14:1107-1119
Mata, Ignacio F; Johnson, Catherine O; Leverenz, James B et al. (2017) Large-scale exploratory genetic analysis of cognitive impairment in Parkinson's disease. Neurobiol Aging 56:211.e1-211.e7
Paul, Kimberly C; Sinsheimer, Janet S; Cockburn, Myles et al. (2017) Organophosphate pesticides and PON1 L55M in Parkinson's disease progression. Environ Int 107:75-81
Mata, Ignacio F; Leverenz, James B; Weintraub, Daniel et al. (2016) GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease. Mov Disord 31:95-102
Paul, Kimberly C; Rausch, Rebecca; Creek, Michelle M et al. (2016) APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression. J Parkinsons Dis 6:349-59
Paul, Kimberly C; Sinsheimer, Janet S; Rhodes, Shannon L et al. (2016) Organophosphate Pesticide Exposures, Nitric Oxide Synthase Gene Variants, and Gene-Pesticide Interactions in a Case-Control Study of Parkinson's Disease, California (USA). Environ Health Perspect 124:570-7
Kannarkat, G T; Cook, D A; Lee, J-K et al. (2015) Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study. NPJ Parkinsons Dis 1:
Lee, P C; Bordelon, Y; Bronstein, J et al. (2015) Head injury, ?-synuclein genetic variability and Parkinson's disease. Eur J Neurol 22:874-8

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