Abstract
We investigated the microglial response to progressive dopamine neuron degeneration using in vivo positron emission tomography (PET) imaging and postmortem analyses in a Parkinson's disease (PD) rat model induced by unilateral (right side) intrastriatal administration of 6-hydroxydopamine (6-OHDA). Degeneration of the dopamine system was monitored by PET imaging of presynaptic dopamine transporters using a specific ligand (11)C-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane). Binding of (11)C-CFT was markedly reduced in the striatum indicating dopaminergic degeneration. Parallel PET studies of (11)C-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3 isoquinoline carboxamide) (specific ligand for activated microglia) showed increased binding in the striatum and substantia nigra indicative of a microglial response. Postmortem immunohistochemical analyses were performed with antibodies against CR3 for microglia/macrophage activation. Using a qualitative postmortem index for microglial activation we found an initially focal, then widespread microglial response at striatal and nigral levels at 4 weeks postlesion. These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD*
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Antigens, Neoplasm*
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Antigens, Surface*
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Antineoplastic Agents / pharmacology
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Avian Proteins*
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Basigin
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Blood Proteins*
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Carbon Radioisotopes
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Dopamine / metabolism*
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Encephalitis / diagnostic imaging*
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Encephalitis / pathology
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Encephalitis / physiopathology
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Gliosis / diagnostic imaging
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Gliosis / pathology
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Gliosis / physiopathology
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Isoquinolines / pharmacology
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Membrane Glycoproteins / metabolism
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Microglia / metabolism*
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Microglia / pathology
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Neostriatum / diagnostic imaging*
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Neostriatum / pathology
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Neostriatum / physiopathology
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Neural Pathways / diagnostic imaging*
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Neural Pathways / pathology
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Neural Pathways / physiopathology
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Neurons / metabolism*
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Neurons / pathology
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Oxidopamine / pharmacology
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Parkinson Disease / diagnostic imaging
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Parkinson Disease / pathology
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Parkinson Disease / physiopathology
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Rats
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Substantia Nigra / diagnostic imaging*
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Substantia Nigra / pathology
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Substantia Nigra / physiopathology
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Sympatholytics / pharmacology
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Tomography, Emission-Computed
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Antigens, CD
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Antigens, Neoplasm
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Antigens, Surface
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Antineoplastic Agents
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Avian Proteins
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Blood Proteins
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Bsg protein, Gallus gallus
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Bsg protein, rat
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Carbon Radioisotopes
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Isoquinolines
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Membrane Glycoproteins
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Sympatholytics
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Basigin
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Oxidopamine
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Tyrosine 3-Monooxygenase
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Dopamine
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PK 11195