SELECTIVE ACID VULNERABILITY OF DOPAMINERGIC-NEURONS AND ITS RECOVERYBY BRAIN-DERIVED NEUROTROPHIC FACTOR

Among the pathogenetic phenomena of Parkinson's disease, the character of the selective degeneration of nigrostriatal system with severe gli osis is not fully understood. Here, we have shown that dopaminergic ne urons may be exclusively sensitive to elevated acidity elicited after the addition of glial mitogenic factors such as epidermal growth facto r and basic fibroblast growth factor or after the direct treatment wit h hydrochloric acid. The acid sensitivity was specific to dopaminergic neurons. The neurons other than dopaminergic neurons in culture from the ventral mesencephalon were not sensitive to acidity and the neuron s from several brain areas were the same as above, except for the hipp ocampal neurons which had slight acid vulnerability. Choline acetyltra nsferase assay studies demonstrated that the cholinergic neuronal popu lation in the septum and corpus striatum had no acid sensitivity. The vulnerability of dopaminergic neurons either elicited by glial mitogen ic factor or derived from the direct acid exposure was inhibited by th e addition of brain-derived neurotrophic factor (BDNF), but not by neu rotrophin-3 or nerve growth factor. These findings suggest that dopami nergic neurons have selective acid vulnerability on which BDNF has a p ronounced protective effect.