Abstract
Ferritin elevation has been reported by some laboratories to occur within the substantia nigra (SN), the area of the brain affected in Parkinson's disease (PD), but whether such an increase could be causatively involved in neurodegeneration associated with the disorder is unknown. Here, we report that chronic ferritin elevation in midbrain dopamine-containing neurons results in a progressive age-related neurodegeneration of these cells. This provides strong evidence that chronic ferritin overload could be directly involved in age-related neurodegeneration such as occurs in Parkinson's and other related diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
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Age Factors
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Aging*
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Animals
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Dopamine / metabolism*
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Exploratory Behavior / physiology
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Ferritins / genetics
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Ferritins / metabolism*
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Fluoresceins
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Gene Expression / genetics
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Humans
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Magnetic Resonance Imaging / methods
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Mice
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Mice, Transgenic
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Nerve Degeneration* / chemically induced
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Nerve Degeneration* / genetics
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Nerve Degeneration* / pathology
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / ultrastructure
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Organic Chemicals / metabolism
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Silver Staining
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Substantia Nigra / pathology*
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Fluoresceins
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Organic Chemicals
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fluoro jade
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Ferritins
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Tyrosine 3-Monooxygenase
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Dopamine