The cholinergic neurotoxin ethylcholine mustard aziridinium (AF64A) induces an increase in MAO-B activity in the rat brain

Abstract

Abstract Recently it was reported that there is an increase in monoamine oxidase B (MAO-B) activity in post-mortem brains of patients with Alzheimer's disease. It was postulated that this increase in MAO-B activity was due gliosis associated with neuronal degeneration. The aim of the present investigation was to evaluate the effect on MAO of nneuronal degeneration primarily affecting the cholinergic system. The specific cholinergic toxin AF64A (3 and 4.5 nmol) was injected bilaterally into the cerebral ventricles of rats. We then estimated MAO-A, MAO-B, dopamine (DA) uptake rates and choline acetyltransferase (ChAT) activities in hippocampus, striatum and cortex 1,2.5 and 4.5 weeks after the injection. Marked long-lasting reduction in ChAT activities appeared only in hippocampus, consistent with previous reports. The MAO-A activity was unchanged as were DA uptake rates. Neither was there any change in MAO-B activity found 1 week after the injection. However, a significant increase in MAO-B activity appeared after 2.5 weeks and persisted after 4.5 weeks in all 3 brain regions investigated. This result is likely to reflect progressive gliosis after cholinergic neuronal degeneration. Previous results have shown an increased MAO-B activity with age and further accelerated increase in Alzheimer's disease. Experimentally, hemitransection and injection of kainic acid have been shown to cause a similar increase. The present results show that changes in MAO-B activity also reflect degenerative processes in brain mainly affecting the cholinergic system.