Selective acid vulnerability of dopaminergic neurons and its recovery by brain-derived neurotrophic factor.
Among the pathogenetic phenomena of Parkinson's disease, the character of the selective degeneration of nigrostriatal system with severe gliosis is not fully understood. Here, we have shown that dopaminergic neurons may be exclusively sensitive to elevated acidity elicited after the addition of glial mitogenic factors such as epidermal growth factor and basic fibroblast growth factor or after the direct treatment with 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 neurons from several brain areas were the same as above, except for the hippocampal neurons which had slight acid vulnerability. Choline acetyltransferase assay studies demonstrated that the cholinergic neuronal population in the septum and corpus striatum had no acid sensitivity. The vulnerability of dopaminergic neurons either elicited by glial mitogenic factor or derived from the direct acid exposure was inhibited by the addition of brain-derived neurotrophic factor (BDNF), but not by neurotrophin-3 or nerve growth factor. These findings suggest that dopaminergic neurons have selective acid vulnerability on which BDNF has a pronounced protective effect.
Akaneya
Y
Y
Department of Neurology, Kinki University School of Medicine, Osaka, Japan.
Takahashi
M
M
Hatanaka
H
H
D000143:Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D020933:Neurotrophin 3; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000143:Acids; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009498:Neurotoxins; D020933:Neurotrophin 3; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D004298:Dopamine