Neuronal ectopic expression of tyrosine hydroxylase in the mouse striatum by combined administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 3-nitropropionic acid.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a dopaminergic neurotoxin which inhibits mitochondrial complex I. 3-Nitropropionic acid (3-NPA) inhibits mitochondrial complex II and produces specific striatal lesions. In order to produce a combined striatal neuronal and dopaminergic afferent lesion, we administered both toxins simultaneously to the mouse. The combination brought about a lesion in the striatum that was not simply additive of the two combined toxins. Intriguingly, a group of striatal neurons became immunoreactive to tyrosine hydroxylase after day 1. Some of them were clearly visible up to the dendritic details. Immuno-electron microscopy indicated that the tyrosine hydroxylase-positive striatal neurons contained densely immunoreactive polyribosomes. Reverse transcriptase-polymerase chain reaction analysis indicated the up-regulation of tyrosine hydroxylase mRNA in the treated striatum. These neurons were also immunoreactive to aromatic L-amino acid decarboxylase.We conclude that the combined administration of MPTP and 3-NPA caused a more profound damage to the nigro-striatal dopaminergic system, and thus some striatal neurons capable of up-regulating tyrosine hydroxylase were induced to produce dopamine, probably to compensate for the dopamine depletion.
Nakahara
T
T
Department of Neurology, School of Medicine, Fukushima Medical University, Hikarigaoka 1, 960-1295, Fukushima, Japan. nack@fmu.ac.jp
Yamamoto
T
T
Endo
K
K
Kayama
H
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000032:analysis; D003292:Convulsants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology*; D003593:Cytoplasm / Q000201:enzymology / Q000648:ultrastructure; D015259:Dopamine Agents / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000648:ultrastructure; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D009574:Nitro Compounds; D020734:Parkinsonian Disorders / Q000503:physiopathology; D011422:Propionates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000235:genetics*
D003292:Convulsants; D015259:Dopamine Agents; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; C015392:3-nitropropionic acid