Behavioral phenotyping of the MPTP mouse model of Parkinson's disease

Sedelis, Marco; Schwarting, Rainer K.W.; Huston, Joseph P.

doi:10.1016/s0166-4328(01)00309-6

Cited by 380 publications

(225 citation statements)

References 126 publications

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“…Whereas a pharmacological validation of the rat dyskinesia model has been provided in a number of previous studies (Lundblad et al, 2002;Dekundy et al, 2003), it has thus far remained unknown whether the mouse AIMs have pharmacological features similar to L-DOPA-induced dyskinesia in PD. This question is highly warranted, because rodent species (and even strains of the same species) can exhibit pronounced differences in brain neurotransmitter activity and DA receptor-mediated control of motor behaviour (Puglisi-Allegra & Cabib, 1997; Sedelis et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia

Lundblad

Usiello

Carta

et al. 2005

Experimental Neurology

173

131

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Section: Discussionmentioning

confidence: 99%

Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia

Lundblad

Usiello

Carta

et al. 2005

Experimental Neurology

173

131

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“…Conversely, the neurochemical and behavioral outcomes of MPTP administration in mice are highly variable, mainly depending on strain, age, gender, route and protocol of administration (Sedelis et al, 2001;Meredith and Kang, 2006). Thus, a direct comparison with data obtained in our model is quite difficult.…”

Section: Role Of Endogenous N/ofq In Modulation Of Mptp-induced Parkimentioning

confidence: 90%

Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism

Viaro

Sánchez‐Pernaute

Marti

et al. 2008

Neurobiology of Disease

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Endogenous nociceptin/orphanin FQ (N/OFQ) inhibits the activity of dopamine neurons in the substantia nigra and affects motor behavior. In this study we investigated whether a N/OFQ receptor (NOP) antagonist, J-113397, can modify movement in naive mice and nonhuman primates and attenuate motor deficits in MPTP-treated parkinsonian animals. J-113397 facilitated motor activity in naïve mice at low doses (0.1-1 mg/kg) and inhibited it at higher ones (10 mg/kg). Likewise, in MPTP-treated mice, J-113397 reversed motor deficit at 0.01 mg/kg but worsened hypokinesia at higher doses (1 mg/kg). In naïve nonhuman primates, J-113397, ineffective up to 1 mg/kg, produced inconsistent motor improvements at 3 mg/kg. Conversely, in parkinsonian primates J-113397 (0.01 mg/kg) reversed parkinsonism, being most effective against hypokinesia. We conclude that endogenous N/OFQ modulates motor activity in mice and nonhuman primates and contributes to parkinsonian symptoms in MPTP-treated animals. NOP receptor antagonists may represent a novel approach to Parkinson's disease.

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“…The pole test has been used in mice previously to assess movement disorders due to striatal dopamine depletion or basal-ganglia abnormality (Fernagut et al, 2003;Fleming et al, 2004;Matsuura et al, 1997;Ogawa et al, 1985;Sedelis et al, 2001). Each mouse (n= ak -60, wt -54) was placed head upwards on top of an inclined (about 60°) wooden pole (1cm diameter and 50cm long) with a cardboard barrier to prevent upward traversal.…”

Section: Pole Test-mentioning

confidence: 99%

Motor deficits and altered striatal gene expression in aphakia (ak) mice

et al. 2007

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Like humans with Parkinsons disease (PD), the ak mouse lacks the majority of the substantia nigra pars compacta (SNc) and experiences striatal denervation. The purpose of this study was to test whether motor abnormalities in the ak mouse progress over time, and whether motor function could be associated with temporal alterations in the striatal transcriptome. Ak and wt mice (28 to 180 days old) were tested using paradigms sensitive to nigrostriatal dysfunction. Results were analyzed using a linear mixed model. Ak mice significantly underperformed wt controls in rotarod, balance beam, string test, pole test and cotton shred tests at all ages examined. Motor performance in ak mice remained constant over the first 6 months of life, with the exception of the cotton shred test, in which ak mice exhibited marginal decline in performance. Dorsal striatal semi-quantitative RT-PCR for 19 dopaminergic, cholinergic, glutaminergic and catabolic genes was performed in 1 and 6 month old groups of ak and wt mice. Preproenkephalin levels in ak mice were elevated in both age groups. Drd1, 3 and 4 levels declined over time, in contrast to increasing Drd2 expression. Additional findings included decreased Chrnα6 expression and elevated VGluT1 expression at both time points in ak mice, and elevated AchE expression in young ak mice only. Results confirm that motor ability does not decline significantly for the first 6 months of life in ak mice. Their striatal gene expression patterns are consistent with dopaminergic denervation, and change over time, despite relatively unaltered motor performance.

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Behavioral phenotyping of the MPTP mouse model of Parkinson's disease

Cited by 380 publications

References 126 publications

Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia

Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia

Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism

Motor deficits and altered striatal gene expression in aphakia (ak) mice

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