Abstract
The inflammatory central nervous system response that involves activated microglia and reactive astrocytes may both heal and harm neurons, as inflammatory mediators lead to neuroprotection or excitation at one dose but to injury at a different concentration. To investigate these complex cellular interactions, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a selective substrate inhibitor of glutamate transport, was infused during 14 days in the rat hippocampus at three different rates: 5, 10 and 25 nmol/h. A microglial reaction appeared at the 5 nmol/h PDC rate in absence of astroglial reaction and neuronal loss. Microgliosis and neuronal death were observed at PDC 10 nmol/h in absence of astrogliosis and calcium precipitation, whereas all four aspects were present at the highest rate. This dissociation between neuronal loss and astroglial reactivity took place in presence of a permanent microglial reaction. These data suggest a specific response of microglia to PDC whose neuronal effects may differ with the infused dose.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Transport System X-AG / antagonists & inhibitors
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Amino Acid Transport System X-AG / metabolism
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Animals
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Astrocytes / drug effects
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Astrocytes / metabolism
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Astrocytes / pathology
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cell Death / drug effects
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Cell Death / physiology
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Dicarboxylic Acids / toxicity
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Encephalitis / chemically induced
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Encephalitis / metabolism*
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Encephalitis / physiopathology
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Gliosis / chemically induced
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Gliosis / metabolism*
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Gliosis / physiopathology
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Glutamic Acid / metabolism*
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Hippocampus / drug effects
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Hippocampus / metabolism*
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Hippocampus / physiopathology
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Male
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Microglia / drug effects
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Microglia / metabolism
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Microglia / pathology
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Nerve Degeneration / chemically induced
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Nerve Degeneration / metabolism*
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Nerve Degeneration / physiopathology
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Neuroglia / drug effects
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Neuroglia / metabolism*
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Neuroglia / pathology
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Neurons / drug effects
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Neurons / metabolism
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Neurons / pathology
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Neurotransmitter Uptake Inhibitors / toxicity
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Pyrrolidines / toxicity
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Rats
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Rats, Wistar
Substances
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Amino Acid Transport System X-AG
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Dicarboxylic Acids
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Neurotransmitter Uptake Inhibitors
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Pyrrolidines
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Glutamic Acid
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pyrrolidine-2,4-dicarboxylic acid
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Calcium