Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons

Parkinson's disease is characterized by a severe loss of dopaminergic neurons resulting in a range of motor deficits. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain with corresponding Parkinsonian...

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Published in:	Brain research. Molecular brain research. Vol. 141; no. 2; pp. 128 - 137
Main Authors:	McKinley, Enid T., Baranowski, Timothy C., Blavo, Delali O., Cato, Candace, Doan, Thanh N., Rubinstein, Amy L.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 30-11-2005 Elsevier
Subjects:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - antagonists & inhibitors Animals Biological and medical sciences Brain - drug effects Brain - pathology Carassius auratus Danio rerio Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dopamine - physiology Dopamine Plasma Membrane Transport Proteins - antagonists & inhibitors Dopamine Plasma Membrane Transport Proteins - biosynthesis Dopamine Plasma Membrane Transport Proteins - deficiency Dopamine Plasma Membrane Transport Proteins - genetics Dopamine transporter Fundamental and applied biological sciences. Psychology Gene Targeting Medical sciences Monoamine Oxidase Monoamine Oxidase Inhibitors - pharmacology Monoamine Oxidase Inhibitors - therapeutic use Morpholines - pharmacology Morpholines - therapeutic use MPTP MPTP Poisoning - pathology MPTP Poisoning - prevention & control Nerve Degeneration - chemically induced Nerve Degeneration - pathology Nerve Degeneration - prevention & control Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Neurodegeneration Neurology Neurons - drug effects Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Nomifensine - pharmacology Nomifensine - therapeutic use Oligodeoxyribonucleotides, Antisense - pharmacology Oligodeoxyribonucleotides, Antisense - therapeutic use Parkinson's disease Primates Selegiline - pharmacology Selegiline - therapeutic use Species Specificity Swimming Tyrosine 3-Monooxygenase - biosynthesis Tyrosine 3-Monooxygenase - genetics Vertebrates: nervous system and sense organs Zebrafish Zebrafish - embryology Zebrafish - growth & development Disorders of the nervous system Zebrafish Dopamine transporter Parkinson's disease MPTP Neurodegeneration Neuroprotection Nervous system diseases Dopamine Toxicity Parkinson disease Catecholamine Cerebral disorder Toxin Vertebrata Brachydanio rerio Pisces Central nervous system disease Neurotoxin Neurotransmitter Dopaminergic neuron Degenerative disease Degeneration Carrier protein Extrapyramidal syndrome
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Summary:	Parkinson's disease is characterized by a severe loss of dopaminergic neurons resulting in a range of motor deficits. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain with corresponding Parkinsonian symptoms. Several animal species have also shown sensitivity to MPTP, including primates, mice, goldfish, and, most recently, zebrafish. This study demonstrates that the effect of MPTP on dopaminergic neurons in zebrafish larvae is mediated by the same pathways that have been demonstrated in mammalian species. MPTP-induced neurodegeneration was prevented by co-incubation with either the monoamine oxidase-B (MAO-B) inhibitor l-deprenyl or the dopamine transporter (DAT) inhibitor nomifensine. Furthermore, targeted inactivation of the DAT gene by antisense morpholinos also protected neurons from MPTP damage. Thus, the mechanism for MPTP-induced dopaminergic neuron toxicity in mammals is conserved in zebrafish larvae. Effects on swimming behavior and touch response that result from MPTP damage are partially ameliorated by both l-deprenyl and DAT knockdown.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0169-328X 1872-6941
DOI:	10.1016/j.molbrainres.2005.08.014