The Effects of Repeated Low-Level Sarin Exposure on Muscarinic M1 Receptor Binding, Amyloid Precursor Protein Levels and Neuropathology
Abstract
The objective of this study was to determine whether there are significant changes in muscarinic M1 receptors (m1AChR), levels of amyloid precursor protein (APP), and neuropathology following repeated exposure to low levels of sarin. Guinea pigs were exposed 5 days/week/two weeks to either saline or one of two sarin doses. Experimental parameters were assessed at five time points: exposure day 10 (E10) and at 3 (P3), 10 (P10), 30 (P30) and 100 (P100) days post-exposure. No difference was observed among groups in either receptor density (Bmax) or receptor affinity (Kd) following cortical m1AChR binding. Western blotting revealed increases in membrane-bound cortical APP levels in both sarin groups at P3, with an increase in only the 0.4 x LD50 group at P30. APP levels were equivalent across groups at P100. H&E staining revealed no brain lesions in either sarin group, and there were no cardiac abnormalities. MAP-2 staining was performed; no difference in staining intensity was observed in either sarin group. Current data suggests that the initial depression of acetylcholinesterase is not of sufficient magnitude and duration to result in persistent neurochemical or neuropathological changes, or in physiological, electroencephalographic, or behavioral alterations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA465925
Entities
People
- John H. McDonough
- Julia K. Penwell
- Mark R. Reynolds
- Melinda R. Roberson
- Robert K. Kan
Organizations
- United States Army Medical Research Institute of Chemical Defense