Assessing the Impact of Acetylcholinesterase (AChE) Inhibition on Cognition and Brain Neurochemistry
Abstract
The proposed studies will conduct toxicologically sensitive cognitive and neurochemical assessments in male and female rats of up to five chemically-diverse AChE inhibitors (e.g., rivastigmine (carbamate), physostigmine (carbamate); donepezil (piperidine derivative), galantamine (phenanthrene alkaloid), tacrine (pyridine derivative)), metrifonate [organophosphateI) to i) establish acute effects (base Year 1), ii) identify countermeasures (option Year 2), iii) determine impact of chronic exposure (option Year 3), and iv) neurocognitive, neurochemical, physiological/molecular studies in rodents or non-human primates based on DTRA S direction (option years 4-5). The overarching goal is to address Thrust Area 7 by conducting focused studies in laboratory animals using a battery of in vivo translational procedures in male and female rats to: 1) determine how acute and chronic exposure to chemical weapons analogues (AChE inhibitors) dysregulate brain neurochemistry to impact cognition. Identifying, abnormalities in key neurochemical signatures in the brain that lead to deterioration of cognitive processes will provide useful translational predictors of the CNS risk associated with acute and chronic exposure to chemical warfare agents; and 2) facilitate the development of improved CNS-related diagnostic biomarkers that will be needed to identify novel pharmacological inteiventions that will effectively counter the harmful effects of acute and chronic exposure to chemical warfare agents.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 08, 2022
- Source ID
- HDTRA12210024
Entities
People
- Rajeev Desai
Organizations
- Defense Threat Reduction Agency
- McLean Hospital