Deleterious effects of minocycline in animal models of Parkinson’s disease and Huntington’s disease.

Elsa Diguet, Pierre-Olivier Fernagut, Xing Wei, Yansheng Du, Richard Rouland, Christian Gross, Erwan Bezard, François Tison
European Journal of Neuroscience. 2004-06-01; 19(12): 3266-3276
DOI: 10.1111/j.0953-816x.2004.03372.x

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1. Eur J Neurosci. 2004 Jun;19(12):3266-76.

Deleterious effects of minocycline in animal models of Parkinson’s disease and
Huntington’s disease.

Diguet E(1), Fernagut PO, Wei X, Du Y, Rouland R, Gross C, Bezard E, Tison F.

Author information:
(1)Physiologie et Physiopathologie de la Signalization Cellulaire, UMR-CNRS 5543,
Université Victor Segalen Bordeaux2, 146 rue Léo Saignat, 33076, Bordeaux,

Minocycline has been shown to exert anti-inflammatory effects underlying its
putative neuroprotective properties in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s
disease and in the R6/2 mouse model of Huntington’s disease (HD). However,
contradictory results have recently been reported. We report deleterious effects
of minocycline in two phenotypic (toxic) models of Parkinson’s disease and HD in
monkey and mouse. Of seven MPTP-intoxicated female cynomolgus monkeys (0.2 mg/kg,
i.v. until day 15), three received minocycline (200 mg b.i.d.). While
placebo-MPTP-treated animals displayed mild parkinsonism at day 15, the
minocycline/MPTP-treated animals tended to be more affected (P = 0.057) and
showed a greater loss of putaminal dopaminergic nerve endings (P < 0.0001). In
the 3-nitropropionic acid (3-NP) mouse model of HD, minocycline (45 mg/kg i.p.)
was administered 30 min before each i.p. injection of 3-NP (b.i.d., cumulated
dose, 360 mg/kg in 5 days). Mice receiving minocycline exhibited a worsening of
the mean motor score with a slower recovery slope, more impaired general activity
and significantly deteriorated performances on the rotarod, pole test and
beam-traversing tasks. The histopathological outcome demonstrated that
minocycline-treated mice presented significantly more severe neuronal cell loss
in the dorsal striatum. The effect of minocycline vs. 3-NP was also investigated
on hippocampal and cortical cell cultures. minocycline blocked 3-NP-induced
neurotoxicity at certain doses (1 mm cortical neurons) but not at higher doses
(10 mm). Thus, minocycline may have variable and even deleterious effects in
different species and models according to the mode of administration and dose.

DOI: 10.1111/j.0953-816X.2004.03372.x
PMID: 15217383 [Indexed for MEDLINE]

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