Abstract
Minocycline has been shown to be neuroprotective in various models of neurodegenerative diseases. However, its potential in Huntington's disease (HD) models characterized by calpain-dependent degeneration and inflammation has not been investigated. Here, we have tested minocycline in phenotypic models of HD using 3-nitropropionic acid (3NP) intoxication and quinolinic acid (QA) injections. In the 3NP rat model, where the development of striatal lesions involves calpain, we found that minocycline was not protective, although it attenuated the development of inflammation induced after the onset of striatal degeneration. The lack of minocycline activity on calpain-dependent cell death was also confirmed in vitro using primary striatal cells. Conversely, we found that minocycline reduced lesions and inflammation induced by QA. In cultured cells, minocycline protected against mutated huntingtin and staurosporine, stimulations known to promote caspase-dependent cell death. Altogether, these data suggested that, in HD, minocycline may counteract the development of caspase-dependent neurodegeneration, inflammation, but not calpain-dependent neuronal death.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calpain / drug effects
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Calpain / metabolism
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Caspases / drug effects
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Caspases / metabolism
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Cell Death / drug effects
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Cell Death / physiology
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Cells, Cultured
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Corpus Striatum / drug effects
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Corpus Striatum / pathology
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Corpus Striatum / physiopathology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Encephalitis / drug therapy
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Encephalitis / physiopathology
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Encephalitis / prevention & control
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Glutamic Acid / metabolism
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Huntingtin Protein
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Huntington Disease / drug therapy*
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Huntington Disease / metabolism
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Huntington Disease / pathology
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Male
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Minocycline / pharmacology*
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Minocycline / therapeutic use
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / pathology
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Nerve Degeneration / prevention & control*
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / metabolism
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Nitro Compounds
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism
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Phenotype
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Propionates
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Quinolinic Acid
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Rats
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Rats, Inbred Lew
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Rats, Wistar
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Staurosporine / antagonists & inhibitors
Substances
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Htt protein, rat
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Huntingtin Protein
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Nerve Tissue Proteins
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Neuroprotective Agents
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Nitro Compounds
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Nuclear Proteins
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Propionates
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Glutamic Acid
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Calpain
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Caspases
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Quinolinic Acid
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Minocycline
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Staurosporine
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3-nitropropionic acid