Evaluation of Early and Prolonged Effects of Acute Neurotoxicity and Neuroprotection Using Novel Functional Imaging Techniques
Abstract
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 using a superThigh resolution positron tomograph to explore acute and long-term excitotoxicity mediated mechanisms in rats exposed to 3-nitroproptiomc 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. We tested also neuroprotection against 3 NP induced neurotoxicity with metabotropic glutamate receptor agonist; ABHxD-I. These studies showed that ABHxD-I could protect during the injection period, but after it, 3-NP induced striatal degeneration continues. Studies of dopamine receptors (Dl and D2) as well as dopamine transporters showed a gradually decreased binding following 3-NP administrations both in protected and non-protected 3-NP rats. In HI) mice, a progressive age related degeneration of glucose metabolism was observed correlating with decrease in N-acetyl-aspartate detected with MRS. Dopamine receptor and transporter bindings were significantly reduced compared to littermate controls. Studies of glutamate receptors showed locally decreased binding in striatum and in cortex following 3-NP. In addition, technical goals of algorithm development for data acquisition, image reconstruction, and data analyses were met.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA407544
Entities
People
- Anna-Liisa Brownell
Organizations
- Massachusetts General Hospital