title: Minocycline in phenotypic models of Huntington's disease.
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.
authors.affiliation: Laboratory of Neurophysiology, ULB-Erasme, Brussels, Belgium.
authors.forename: Kadiombo
authors.initials: K
authors.lastname: Bantubungi
authors.forename: Carine
authors.initials: C
authors.lastname: Jacquard
authors.forename: Anita
authors.initials: A
authors.lastname: Greco
authors.forename: Annita
authors.initials: A
authors.lastname: Pintor
authors.forename: Abdelwahed
authors.initials: A
authors.lastname: Chtarto
authors.forename: Khalid
authors.initials: K
authors.lastname: Tai
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Galas
authors.forename: Liliane
authors.initials: L
authors.lastname: Tenenbaum
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.forename: Patrizia
authors.initials: P
authors.lastname: Popoli
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Brouillet
authors.forename: Jacques
authors.initials: J
authors.lastname: Brotchi
authors.forename: Marc
authors.initials: M
authors.lastname: Levivier
authors.forename: Serge N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: David
authors.initials: D
authors.lastname: Blum
mesh_terms: D000818:Animals; D002154:Calpain / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018698:Glutamic Acid / Q000378:metabolism; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009574:Nitro Compounds; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010641:Phenotype; D011422:Propionates; D017378:Quinolinic Acid; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D019311:Staurosporine / Q000037:antagonists & inhibitors
chemical_list: C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D009687:Nuclear Proteins; D011422:Propionates; D018698:Glutamic Acid; D002154:Calpain; D020169:Caspases; D017378:Quinolinic Acid; D008911:Minocycline; D019311:Staurosporine; C015392:3-nitropropionic acid