Neuronal Degeneration in the Cingulate Gyrus: NMDA Antagonists and Anticholinesterases
Abstract
The goal of this study is to understand the interact ion between drugs that are antagonists at the NMDA receptor subtype of glutamate receptors and drugs that are anticholinesterases. Previous research showed that NMDA antagonists are neurotoxic in the cingulate/retrosplenial cortex and that this toxicity was enhanced by muscarinic cholinergic agonists. We hypothesized that anticholinesterases would also enhance the toxicity of these compounds. We have used three approaches in this study: (1) We used intracellular electrophysiology; (2) We used imaging of brain slices treated with voltage sensitive dyes; and (3) We used a stain (Fluro-Jade) which identifies dying neurons. Each of these approaches showed that NMDA antagonism produces excitability and/or neurotoxicity in these brain areas. Surprisingly, the anticholinesterase pyridostigmine appears to be inhibitory and preliminary studies suggest that it may protect against NMDA antagonist neurotoxicity. Our second year of experiments will continue this line of research.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA385678
Entities
People
- Wilkie A. Wilson
Organizations
- Duke University Hospital