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The Journal of Neuroscience, October 15, 2002, 22(20):8951-8960
Methamphetamine-Induced Degeneration of Dopaminergic Neurons
Involves Autophagy and Upregulation of Dopamine Synthesis
Kristin E.
Larsen1,
Edward A.
Fon2,
Teresa G.
Hastings3,
Robert H.
Edwards4, and
David
Sulzer1
1 Departments of Neurology and Psychiatry, Columbia
University, and Department of Neuroscience, New York Psychiatric
Institute, New York, New York 10032, 2 Centre for Neuronal
Survival, Montreal Neurological Institute, McGill University, Montreal,
Quebec H3A 2B4, Canada, 3 Departments of Neuroscience and
Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and 4 Departments of Neurology and Physiology, University
of California, San Francisco, California 94143
Methamphetamine (METH) selectively injures the neurites of dopamine
(DA) neurons, generally without inducing cell death. It has been
proposed that METH-induced redistribution of DA from the vesicular
storage pool to the cytoplasm, where DA can oxidize to produce quinones
and additional reactive oxygen species, may account for this selective
neurotoxicity. To test this hypothesis, we used mice heterozygous
(+/ ) or homozygous (/) for the brain vesicular monoamine uptake
transporter VMAT2, which mediates the accumulation of cytosolic DA into
synaptic vesicles. In postnatal ventral midbrain neuronal cultures
derived from these mice, METH-induced degeneration of DA neurites and
accumulation of oxyradicals, including metabolites of oxidized DA,
varied inversely with VMAT2 expression. METH administration also
promoted the synthesis of DA via upregulation of tyrosine hydroxylase
activity, resulting in an elevation of cytosolic DA even in the absence
of vesicular sequestration. Electron microscopy and fluorescent
labeling confirmed that METH promoted the formation of autophagic
granules, particularly in neuronal varicosities and, ultimately, within
cell bodies of dopaminergic neurons. Therefore, we propose that METH
neurotoxicity results from the induction of a specific cellular pathway
that is activated when DA cannot be effectively sequestered in synaptic
vesicles, thereby producing oxyradical stress, autophagy, and neurite degeneration.
Key words:
methamphetamine; VMAT2; oxidative stress; neurodegeneration; dopamine; ventral midbrain; autophagy
Copyright © 2002 Society for Neuroscience 0270-6474/02/22208951-10$05.00/0
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|
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|
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|
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|
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|
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|
|
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|
|
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|
|
|
|
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24(26):
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|
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|
|
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|
|
|
|
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|
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|
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|
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|
|
|
|
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100(19):
11035 - 11040.
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|
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|
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J. Neurosci.,
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23(13):
5835 - 5845.
[Abstract]
[Full Text]
[PDF]
|
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|
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