Evaluation of Early and Prolonged Effects of Acute Neurotoxicity and Neuroprotection Using Novel Functional Imaging Techniques
Abstract
Increasing environmental toxicity has been significantly linked either directly, or indirectly, to the etiology of neurodegenerative diseases. We have proposed to explore the relationship between impairments in functional and metabolic pathways and regional neural dysfunction, and the efficacy of neuroprotection provided by a metabotropic glutamate receptor agonist. We have conducted studies of dopamine receptors, reuptake sites, metabotropic glutamate receptors and glucose metabolism using a super-high resolution positron tomograph to explore acute and long-term excitotoxicity mediated mechanisms in rats exposed to 3-nitroproprionic acid (3-NP). We have also conducted studies of glucose metabolism in transgenic mice expressing Huntington's gene. Complementary magnetic resonance spectroscopy studies to explore changes in neurochemicals were conducted in both 3-NP treated rats and transgenic mice as well. A significant amount of biological information has been obtained regarding 3-NP induced degenerative changes in energy metabolism and dopaminergic regulation. Interanimal variability of motor activity and glucose metabolism in response to 3-NP continue. Studies of dopamine receptors (D1 and D2) showed a gradual decrease following 3-NP administration. An early increase in dopamine transporter binding to presynaptic terminals was observed immediately after 3-NP, followed by a gradual decrease. Studies of glutamate receptors showed locally decreased binding in striatum and in cortex following 3-NP. Reversible early increases of lactate and succinate in MRS were observed as well. In addition, technical goals of al algorithm development for data acquisition, image reconstruction, and data analyses were met.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA396368
Entities
People
- Anna-Liisa Brownell