Pyridostigmine-Induced Neurodegeneration: Role of Neuronal Apoptosis.
Abstract
Pyridostigmine causes apoptotic cell destruction in rat brain. The present study reveals mechanisms by which pyridostigmine may cause neuronal death. Pyridostigmine-induced apoptosis is mediated by at least two different receptors in cell cultures from brains of rat pups. Pretreatment of cerebellar granule cells with muscarinic or NMDA receptor blockers attenuates pyridostigmine-induced apoptosis. Both these receptors also mediate increases in reactive oxygen species and calcium in granule cells exposed to pyridostigmine. Elevated intracellular calcium appears to lead to formation of reactive oxygen species since generation of free radicals is inhibited in cells in calcium free media. The reactive oxygen species in turn appear to initiate the apoptotic cell death process, since antioxidants decrease cell destruction by pyridostigmine. These in vitro results suggest that oxidative stress is a factor which causes apoptotic brain cell destruction in certain individuals after pyridostigmine administration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA377168
Entities
People
- Gary Isom
Organizations
- Purdue Research Foundation