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Mesencephalic Dopamine Neurons Become Less Sensitive to 1 ‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine Toxicity During Development In Vitro
Author(s) -
Danias Peter,
Nicklas William J.,
Ofori Senyo,
Shen Julia,
Mytilineou Catherine
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07408.x
Subject(s) - mptp , dopamine , dopaminergic , neurotoxicity , rotenone , neurotoxin , in vitro , biology , monoamine oxidase , toxicity , endocrinology , chemistry , medicine , biochemistry , mitochondrion , enzyme
The in vitro development of monoamine oxidase (MAO) activity and [ 3 H]dopamine (DA) uptake capacity of dissociated cell cultures from rat embryo mesencephalon were correlated with the potency of l‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and l‐methyl‐4‐phenylpyridine (MPP + ) neurotoxicity. Specific activities of both MAO‐A and MAO‐B increased during in vitro development of the cultures, with MAO‐B activity increasing 20‐fold between the first and fourth week. Similarly, [ 3 H]DA accumulation increased 2.6‐fold between the first and third week in vitro, when it reached a plateau. Unexpectedly, the toxicities of MPTP and MPP + were substantially decreased in the older cultures. Exposure to MPTP reduced [ 3 H]DA accumulation per culture by 77% in 1‐week‐old cultures and by 36% in 4‐week‐old cultures. Similarly, damage caused by MPP + was reduced from 84% of control in the first week to 34% of control in the fourth week. The attenuation of neurotoxicity was not due to an increase in storage of MPP + in the synaptic vesicles of DA neurons, nor to a change in the distribution of MPP + between dopaminergic and other cellular components of the cultures. The damage to DA neurons caused by the mitochondrial toxin, rotenone, also showed a similar reduction in the older cultures. These observations coupled with an increase in lactate formation and glucose consumption during the in vitro development of the cultures suggest a shift toward increased glycolysis and decreased dependence on aerobic metabolism. This would render the cells more resistant to the inhibition of mitochondrial function by MPP + .