Unraveling substantia nigra sequential gene expression in a progressive MPTP-lesioned macaque model of Parkinson’s disease.
Neurobiology of Disease. 2005-10-01; 20(1): 93-103
Read on PubMed
1. Neurobiol Dis. 2005 Oct;20(1):93-103.
Unraveling substantia nigra sequential gene expression in a progressive
MPTP-lesioned macaque model of Parkinson’s disease.
Bassilana F(1), Mace N, Li Q, Stutzmann JM, Gross CE, Pradier L, Benavides J,
Ménager J, Bezard E.
(1)Sanofi-Aventis, Vitry sur Seine, France.
Taking advantage of a progressive nonhuman primate model mimicking Parkinson’s
disease (PD) evolution, we monitored transcriptional fluctuations in the
substantia nigra using Affymetrix microarrays in control (normal), saline-treated
(normal), 6 days-treated (asymptomatic with 20% cell loss), 12 days-treated
(asymptomatic with 40% cell loss) and 25 days-treated animals (fully parkinsonian
with 85% cell loss). Two statistical methods were used to ascertain the
regulation and real-time quantitative PCR was used to confirm their regulation.
Surprisingly, the number of deregulated transcripts is limited at all time points
and five clusters exhibiting different profiles were defined using a hierarchical
clustering algorithm. Such profiles are likely to represent
activation/deactivation of mechanisms of different nature. We briefly speculate
about (i) the existence of yet unknown compensatory mechanisms is unraveled, (ii)
the putative triggering of a developmental program in the mature brain in
reaction to progressing degeneration and finally, (iii) the activation of
mechanisms leading eventually to death in final stage. These data should help
development of new therapeutic approaches either aimed at enhancing existing
compensatory mechanisms or at protecting dopamine neurons.
PMID: 16137570 [Indexed for MEDLINE]