Overview
The mouse BIRN Alpha Synuclein mouse model of Parkinson's Disease is a collaborative project spearheaded by Diana Price at NCMIR with Dr. Eliezer Masliah and colleagues at UCSD.
Goals
Our overall goal is to characterize a mouse model of Parkinsonism using a multidisciplinary approach -- including multi-scale imaging technologies, molecular and cellular techniques, behavioral pharmacology and bioinformatics.
These techniques will allow us to establish baseline measurements of CNS markers and behavioral deficits for subsequent preclinical testing of putative therapeutics.
Planning
Plans and Action Items
Working Pages
- Links to related working pages
Minutes, etc.
- Project presentation from 2005 Mouse BIRN AHM (pdf below).
Other important information and links
- Links to areas of interest to the topic
Updates/Progress
The original goals of this collaborative project were to conduct multi-scale studies of a mouse model of Parkinsonian Syndrome and to use this model to establish Parkinson’s as one of the pioneering animal models of neurodegenerative disorders in the NIH Biomedical Informatics Research Network (BIRN) data sharing and collaborative system. Not only has this collaborative research group made novel observations relevant to the study of the etiology and treatment of Parkinson’s disease, but we have also made significant progress in the area of bioinformatics, correlating animal models with human disease. During the first phase of the Mouse BIRN project, using the Parkinson’s model as a driver, we accomplished the following:
- We confirmed the original findings of alpha-synuclein immunoreactivity in transgenic animals overexpressing alpha-synuclein. We confirmed and extended to additional areas using the high-resolution large scale imaging methods developed to fill in missing spatial scales of the multi-scale mouse BIRN project.
- We established experimental protocols for imaging experiments to ensure collection of metadata for database integration.
- We conducted a small scale MRI study with Duke CIVM and UCSD researchers to evaluate usefulness of conducting a larger study.
- Large-scale mosaic image and MRI data were integrated into UCSD and Duke CIVM databases.
- Multi-modal behavioral data were collected including measures of motor and cognitive behavior with relevance to PD.
During the 2005 funding period, we have continued to make substantive progress towards the original project goals. The procedures developed and “best practice” lessons learned during the initial funding period have allowed us to accelerate our progress during the first year of the renewal. Some major highlights of this project include:
- September 2005: A large scale MRI imaging study, with improved resolution and contrast, was conducted and conjunction with Duke-CIVM researchers. These data are being processed and analyzed using methods and tools developed as part of the BIRN project.
- Throughout 2005: Continued characterization of neurotransmitter receptor distributions, which revealed significant alterations in mGluR5 and dopamine D1/D2 receptor immunoreactivity in alpha-synuclein transgenic animals CNS regions compared with non-transgenic control animals.
- Ongoing progress : Continued integration of large-scale image and MRI data into BIRN databases and development of data mediation tools, which allow us to search for and analyze project data in distributed databases (ex. confocal images in CCDB and MRI volumes at Duke).
- Ongoing progress: Disease process maps and ontologies specific to Parkinson’s disease were developed.
- July 2005: New parnerships and communication with other Parkinson’s disease researchers, particularly relevant to the molecular mechanisms of alpha-synuclein aggregation and to symptomatic treatment of patients using new compounds. For the latter we’re validating the mouse model with regard to similarity to the human disorder to allow the mouse to be used as a preclinical base for testing a new drug.
- January 2006- Manuscript published : Describes the mosaic image producing technique used to examine molecules related to Parkinson’s Disease. Price DL, Chow SK, MacLean? NAB, Hakozaki H, Peltier S, Martone ME, Ellisman MH (2006) High-Resolution Large-Scale Mosaic Imaging using Multiphoton Microscopy to Characterize Transgenic Mouse Models of Human Neurological Disorders. Neuroinformatics 4(1):65-80.
- September 2005: Confocal imaging revealed a difference in dopamine D1 receptor immunolabeling in transgenic mice. These results will be presented at the upcoming ICAD meeting in Madrid, Spain by Diana Price. We are extending our observations to additional dopamine receptors.
Our goals for the next project period include (with targeted date for progress/completion):
- June 1, 2006: Submit mGluR5-related manuscript.
- June 15, 2006: Submit funding renewal application to Branfman Family Foundation.
- July 1, 2006: Generate average atlas from T1 weighted MRI volumes.
- August 1, 1006: Complete segmentation of average atlas.
- August 15, 2006: Warp segmentations from average atlas back to original MRI volumes.
- September 1, 2006: Complete segementation edits.
- September 15, 2006: Complete all analyses, draft manuscript outline.
In addition, we have the following plans for project mGluR5 immunolableing data subsequent to publication:
- 4 large scale mosaic images (2 non-tg and 2 tg)
- 128 confocal datasets (8/8 non-tg/tg x 8 ROIs)
- Behavioral data (1 watermaze and a pole test dataset per animal)
- Western blot datasets (representing 8 animals x 3 regions x 2 fractions)
- Data are currently being integrated into the CCDB and will be made freely available to the public upon manuscript publication.
101705_MouseBIRN_PD_DLP.pdf