Genes regulated in MPTP-treated macaques and human Parkinson’s disease suggest a common signature in prefrontal cortex.
Neurobiology of Disease. 2010-06-01; 38(3): 386-394
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1. Neurobiol Dis. 2010 Jun;38(3):386-94. doi: 10.1016/j.nbd.2010.02.008. Epub 2010
Genes regulated in MPTP-treated macaques and human Parkinson’s disease suggest a
common signature in prefrontal cortex.
Storvik M(1), Arguel MJ, Schmieder S, Delerue-Audegond A, Li Q, Qin C, Vital A,
Bioulac B, Gross CE, Wong G, Nahon JL, Bezard E.
(1)Department of Biosciences, Department of Neurobiology, Department of
Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland.
The presymptomatic phase of Parkinson’s disease (PD) is now recognized as a
prodromal phase, with compensatory mechanism masking its progression and
non-motor early manifestations, such as depression, cognitive disturbances and
apathy. Those mechanisms were thought to be strictly dopamine-mediated until
recent advances have shed light upon involvement of putative outside-basal
ganglia, i.e. cortical, structures. We took advantage of our progressive
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model to
monitor whole genome transcriptional changes in several brain areas. Our data
reveals that transcriptomic activity changes take place from early stages,
suggesting very early compensatory mechanisms or pathological activity outside
the basal ganglia, including the PFC. Specific transcriptomic changes occurring
in the PFC of fully parkinsonian MPTP-treated macaques have been identified.
Interestingly, a large part of these transcriptomic changes were also observed in
human post-mortem samples of patients with neurodegenerative diseases analysed by
quantitative PCR. These results suggest that the PFC is able to detect the
progression of dopamine denervation even at very early time points. There are
therefore mechanisms, within the PFC, leading to compensatory alterations and/or
participating to pathophysiology of prodromal PD manifestations.
PMID: 20206263 [Indexed for MEDLINE]