title: Failure of neuronal protection by inhibition of glial activation in a rat model of striatonigral degeneration.
abstract: Previous studies in rodent models of neurodegenerative disorders have demonstrated that minocycline exerts neuroprotective effects unrelated to its antimicrobial action. The purpose of the present study was to analyze whether minocycline exhibits neuroprotective activity in a rat model of striatonigral degeneration (SND), the core pathology underlying levodopa-unresponsive parkinsonism associated with multiple system atrophy (MSA). We observed no significant effect of minocycline on locomotor impairment in double-lesioned SND rats. Minocycline significantly suppressed astroglial and microglial activation (P < 0.01); however, 3'5'-monophosphate-regulated phosphoprotein (DARPP 32) immunohistochemistry revealed no significant differences in striatal lesion volume of minocycline-treated versus untreated control SND rats. Furthermore, there was no protection of nigral dopaminergic neurons in the double-lesion model. We conclude that despite its astrocytic and microglial suppression, minocycline failed to attenuate lesion-induced neuronal damage in the SND rat model.
authors.affiliation: Neurodegeneration Research Laboratory, Innsbruck MSA Study Group, Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. nadia.stefanova@uibk.ac.at
authors.forename: Nadia
authors.initials: N
authors.lastname: Stefanova
authors.forename: Monika
authors.initials: M
authors.lastname: Mitschnigg
authors.forename: Imad
authors.initials: I
authors.lastname: Ghorayeb
authors.forename: Elsa
authors.initials: E
authors.lastname: Diguet
authors.forename: Felix
authors.initials: F
authors.lastname: Geser
authors.forename: Francois
authors.initials: F
authors.lastname: Tison
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020955:Striatonigral Degeneration / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline