PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9364513

Thalidomide reduces MPTP-induced decrease in striatal dopamine levels in mice.

A Boireau·F Bordier·P Dubédat·C Pény·A Impérato
View original source ↗Export metadata ↓

Abstract

The effects of thalidomide, a sedative, anti-inflammatory and immunosuppressive agent were studied in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) murine model of Parkinson's disease. The striatal levels of dopamine (DA) and of its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured both in the MPTP control group (3 x 15 mg/kg intraperitoneally) and in the thalidomide groups (repeated treatments at 25 mg/kg or 50 mg/kg postoperatively). For mice treated with thalidomide, a dose-dependent protection was observed against the MPTP-induced decrease in DA. The decrease in HVA levels was totally antagonized by thalidomide at both doses. That thalidomide has activity in this model suggests that an inflammatory process may be involved in the induction of lesions by MPTP in DAergic neurons.

Explore related subjects

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine3,4-Dihydroxyphenylacetic AcidAnimalsAnti-Inflammatory AgentsCorpus StriatumDisease Models, AnimalDopamineDose-Response Relationship, DrugHomovanillic AcidHypnotics and SedativesImmunosuppressive AgentsMaleMiceMice, Inbred C57BLParkinson DiseaseThalidomideJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Boireau, F Bordier, P Dubédat, C Pény, A Impérato. 1997-10-03. Thalidomide reduces MPTP-induced decrease in striatal dopamine levels in mice.. https://doi.org/10.1016/s0304-3940(97)00685-x

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1998

Opiate receptor avidity is reduced in non-motor impaired MPTP-lesioned rhesus monkeys.

Opiate receptor avidity, roughly equivalent to the ratio of unoccupied receptor density to the receptor dissociation constant (B'max/KD), was measured in four MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine)-lesioned rhesus monkeys and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. Although the MPTP-lesioned monkeys were dopamine deficient as measured with [18F]-L-fluorodopa ([18F]-DOPA) and PET [Doudet et al., 6-[18F]-L-DOPA imaging of the dopamine neostriatal system in normal and clinically normal-MPTP-treated rhesus monkeys, Exp. Brain Res. 78 (1989) 69-80], they had clinically recovered from the acute motor effects of MPTP exposure. Opiate receptor avidity was found to be reduced by 30-35% in the opiate-receptor rich areas of caudate, anterior putamen, thalamus, and amygdala of the MPTP-lesioned animals. The results suggest that opiate pathways make a significant contribution to the adjustment of cortico-striatal-thalamic pathway activity and thereby to behavior in rhesus monkeys following dopamine loss.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

A novel MPTP primate model of Parkinson's disease: neurochemical and clinical changes.

Positron emission tomography (PET) and the dopamine (DA) metabolism tracer, [18F]6-fluoro-L-m-tyrosine (FMT) were used to evaluate the relationship between DA metabolism and the clinical stage of parkinsonism monkeys following either unilateral ICA MPTP infusion or unilateral ICA MPTP infusion and subsequent varying sequential systemic doses of MPTP. Clinical stage corresponded to PET measures of striatal DA metabolism, showing the usefulness of the overlesioned hemiparkinsonian monkey as a stable model of various stages of Parkinson's disease (PD).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatments.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a preferentially selective neurotrophic factor for dopamine (DA) neurons. In the present study, we have examined the distribution of GDNF mRNA expression in several major DA-containing cell body and terminal areas and the regulation of GDNF mRNA expression upon various pharmacological treatments. Results indicated that there is a relatively higher GDNF mRNA level in neurons of the nigrostriatal and mesolimbic dopaminergic pathways. Upon chronic 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/ kg, i.p., for 7 days), DA level was decreased, whereas GDNF mRNA expression was increased in the striatum, suggesting that more GDNF is synthesized and expressed to cope with the neurotoxin insult. Furthermore, among several DA neuron protective and/or therapeutic agents examined, both intrastriatal injections of (-)-deprenyl (1.25 microg and 2.5 microg) and melatonin (30 microg, 60 microg, and 120 microg) significantly enhanced GDNF mRNA expression in the striatum, whereas the same concentrations of (-)-deprenyl did not affect monoamine oxidase B (MAOB) activity, although it increased glutathione peroxidase (GPx) and/or superoxide dismutase (SOD) activities. Similarly, the same concentrations of melatonin did not alter SOD or GPx activities, except that the highest dose of melatonin (120 microg) increased lipid peroxidation in the striatum. Conversely, GM1 ganglioside injection (45 microg) lacked of an effect on GDNF mRNA expression. Together, these results suggest that both (-)-deprenyl and melatonin up-regulate GDNF gene expression at threshold doses lower than that needed for altering MAOB activity and/or the antioxidant enzyme systems, respectively. These results provide new information on the neuroprotective and therapeutic mechanisms of (-)-deprenyl and melatonin on DA neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗