Unraveling substantia nigra sequential gene expression in a progressive MPTP-lesioned macaque model of Parkinson's disease

Bassilana, Frédéric; Mace, Nathalie; Li, Q.; Stutzmann, Jean‐Marie; Gross, Ch.; Pradier, Laurent; Bénavidès, J.; Ménager, Jean; Bézard, Erwan

doi:10.1016/j.nbd.2005.02.005

Cited by 28 publications

(19 citation statements)

References 34 publications

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“…In addition to its neuroprotective role against behavioral and biochemical effects of amyloid toxicity in murine models of AD [24], upregulation of Ttr was found in response to nicotine, which may protect against PD as suggested by epidemiological data [57] and in the SNc of monkeys treated with MPTP before the appearance of symptoms i.e. before the occurrence of cell death [58]. Together these data and our result suggest that Dhcr24 and Ttr may represent antiapoptotic pathway activated by SNCA overexpression.…”

Section: Resultsmentioning

confidence: 99%

Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

Cabeza-Arvelaiz

Fleming

Richter

et al. 2011

Mol Neurodegeneration

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BackgroundAlpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson's disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD.ResultsThe present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis.ConclusionThe results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA.

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Section: Resultsmentioning

confidence: 99%

Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

Cabeza-Arvelaiz

Fleming

Richter

et al. 2011

Mol Neurodegeneration

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“…Transcriptome analysis revealed alterations in the expression of more than 100 genes following dopamine denervation and LID installation (Bassilana et al, 2005;Konradi et al, 2004). So, why Nur77 represents an interesting candidate in dyskinesias?…”

Section: Discussionmentioning

confidence: 99%

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

Mahmoudi

Samadi

Gilbert

et al. 2009

Neurobiology of Disease

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We have previously shown that docosahexaenoic acid (DHA) significantly reduced L-Dopainduced 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 γ1 (RXRγ1), a putative brain receptor for DHA and transcriptional partner of Nur77, in MPTP monkeys treated with L-Dopa and DHA. The RXRγ1 mRNA is strongly expressed in monkey caudate nucleus and putamen, but no change in levels of RXRγ1 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 placed 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 caudateputamen, 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 nonhuman primate model of Parkinson's disease, and suggest that strong modulation of Nur77 expression might be linked to a reduced risk to develop LIDs.

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“…These results indicate that sex differences in toxin-induced cell loss are not hormonally generated and that hormone-dependent changes in striatal DA depletion can occur independently of cell survival. To understand this apparent dissociation of hormonal effects at the cell body and nerve terminals, it is important to appreciate that the damaged neurons and associated basal ganglia circuitry have a remarkable capacity for compensation both in experimental and clinical PD, such that overt motor symptoms may not be apparent until around 80% of striatal dopamine and 60% of SNc perikarya are lost Song and Haber, 2000;Bezard et al, 2003;Bassilana et al, 2005). These adaptive mechanisms include increased synthesis, metabolism, and release of DA per impulse, which restore functionality in the partially damaged NSDA system.…”

Section: Gonadal Factors Are Protective In Female But Not In Male Ementioning

confidence: 99%

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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Unraveling substantia nigra sequential gene expression in a progressive MPTP-lesioned macaque model of Parkinson's disease

Cited by 28 publications

References 34 publications

Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

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

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

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