Y. Akaneya et al., SELECTIVE ACID VULNERABILITY OF DOPAMINERGIC-NEURONS AND ITS RECOVERYBY BRAIN-DERIVED NEUROTROPHIC FACTOR, Brain research, 704(2), 1995, pp. 175-183
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.