Pyridostigmine-Induced Neurodegeneration: Role of Neuronal Apoptosis

摘要

Pyridostigmine produces subtle degeneration of brain cells when given to rats twice daily for 4 days. Apoptotic brain cell damage can be detected throughout the cerebral cortex and in the striatum and hippocampus with higher doses. The process of apoptotic cell death initiated by pyridostigmine continues after treatment with this drug is terminated. Atropine is able to prevent the destruction of brain cells by pyridostigmine, both in vivo and in cultured brain cells. Oxidative stress appears to be an important initiating event since antioxidants can block the increase in reactive oxygen species as well as the cell damage caused by pyridostigmine. Furthermore, blockade of NMDA type glutamate receptors also decreases reactive oxygen species and apoptosis after pyridostigmine treatment of cultured brain cells. Oxidative species lead to activation of redox-sensitive transcription factors, decrease in mitochondrial membrane potential, cytochrome c release and caspase-3 activation, all of which are involved in the process of pyridostigmine-induced destruction of brain cells.