Pyridostigmine-Induced Neurodegeneration: Role of Neuronal Apoptosis
Annual rept. 25 Sep 97-24 Sep 98
PURDUE UNIV LAFAYETTE IN
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Although pyridostigmine is a highly charged molecule, some reports suggest it can penetrate into the brain. To determine whether the drug can cause neurotoxic damage centrally, pyridostigmine was injected into rats, the animals were sacrificed at intervals after drug administration and brains examined histologically. Using TUNEL staining and electron microscopy, apoptotic brain cell destruction was noted in cerebral cortex and at higher doses, cell damage was also noted in striatum and hippocampus. Pretreatment with atropine prevented pyridostigmine induced brain cell apoptosis, showing the involvement of muscarinic receptors. However, antioxidants did not block pyridostigmine-induced apoptosis suggesting that oxidative mechanisms are not involved. Even up to 30 days after injection of pyridostigmine, apoptotic cell death was still evident in rat cortex. Therefore the cell death process initiated by physostigmine continues long after termination of drug treatment. These observations are important because they implicate physostigmine as a causative factor in the Gulf War Syndrome.
- Anatomy and Physiology