Effects of a unilateral stereotaxic injection of Tinuvin 123 into the substantia nigra on the nigrostriatal dopaminergic pathway in the rat.
Tinuvin 123, a compound used in the manufacture of plastics, has recently been suggested to possibly cause Parkinson's disease (PD). Herein, we revisited this issue by assessing the effect of Tinuvin 123 on dopaminergic neurons of the substantia nigra following its stereotaxic injection in the rat. Twenty-one days post unilateral stereotaxic injection of Tinuvin 123, systemic injection of both apomorphine and amphetamine caused rotations toward the side of the lesion in these rats. Tinuvin 123 produced a small to moderate dose-dependent reduction in striatal levels of dopamine and metabolites on the side of the lesion. This compound also produced dramatic cell loss in the substantia nigra on the side of the lesion. However, the loss of cells lacked the phenotypic specificity for tyrosine hydroxylase (TH)-positive neurons that is expected with a dopaminergic neurotoxin. Indeed, aside from a robust glial reaction, both TH-positive and glutamic acid dehydrogenase (GAD)-positive neurons were destroyed, and near the site of the injection, there was complete tissue destruction. This study indicates that, using this mode of injection, Tinuvin 123 exerts a dramatic tissue toxicity without any evidence of specificity for dopaminergic neurons. Thus, our data argues against a role for Tinuvin 123 as an environmental toxin causing a clinical condition characterized by the selective loss of dopaminergic neurons as seen in PD.
Jackson-Lewis
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Columbia University, Department of Neurology, Neuroscience Research, New York, NY 10032, USA. vrj1@columbia.edu
Liberatore
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D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000633:toxicity*; D003652:Decanoic Acids / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D016273:Occupational Exposure / Q000009:adverse effects; D010302:Parkinson Disease, Secondary / Q000473:pathology; D010880:Piperidines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology; D015996:Survival Rate; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002121:Calcium Channel Blockers; D003652:Decanoic Acids; D004785:Environmental Pollutants; D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D010880:Piperidines; C083752:Tinuvin 770; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; D004298:Dopamine