Nur77 mRNA levels and L-Dopa-induced dyskinesias in MPTP monkeys treated with docosahexaenoic acid

NEUROBIOLOGY OF DISEASE

卷:36

Article

Mahmoudi, Souha¹  Samadi, Pershia^2,3  Gilbert, Francois^4,5  Ouattara, Bazoumana^2,3  Morissette, Marc^2,3  Gregoire, Laurent^2,3  Rouillard, Claude^4,5  Di Paolo, Therese^2,3  Levesque, Daniel¹ 

[1] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada

[2] Univ Laval, Mol Endocrinol & Genom Res Ctr, CRCHUQ, Quebec City, PQ, Canada

[3] Univ Laval, Fac Pharm, Quebec City, PQ, Canada

[4] Univ Laval, Neurosci Unit, CRCHUQ, Quebec City, PQ, Canada

[5] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada

关键词: NGFI-B;    NR4A1;    DHA;    Retinoid X receptor (RXR);    MPTP-treated monkey;    Parkinson's disease;    L-Dopa-induced dyskinesia (LID);    Substance P;    Basal ganglia;    Caudate nucleus;    Putamen;    Striatum;   

DOI  :  10.1016/j.nbd.2009.07.017

来源: Elsevier

【 摘 要 】

We have previously shown that docosahexaenoic acid (DHA) significantly reduced L-Dopa-induced dyskinesia (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys (Samadi et al., Ann. Neurol. 59:282-288, 2006). In the present study, we measured for the first time mRNA levels of Nur77, an orphan nuclear receptor that participates to adaptive and/or aberrant dopamine-related behaviors, and retinoid X receptor gamma 1 (RXR gamma 1), a putative brain receptor for DHA and transcriptional partner of Nur77, in MPTP monkeys treated with L-Dopa and DHA. The RXR gamma 1 mRNA is strongly expressed in monkey caudate nucleus and putamen, but no change in levels of RXR gamma 1 was observed following MPTP and L-Dopa treatments. On the other hand, denervation reduced Nur77 mRNA levels, whereas chronic L-Dopa treatment strongly induced Nur77 transcripts. These modulations are taking place in substance P positive cells and are associated with both caudate-putamen matrix and striosome compartments. Interestingly, combination of L-Dopa with DHA further increases Nur77 mRNA levels in the anterior caudate-putamen, and mainly in striosomes. This is accompanied by a significant inverse correlation between Nur77 mRNA levels and dyskinetic scores. Taken together, our results show that Nur77 expression is modulated following dopamine denervation and chronic L-Dopa therapy in a non-human primate model of Parkinson's disease, and suggest that strong modulation of Nur77 expression might be linked to a reduced risk to develop LIDs. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

Free