III. Primate model of parkinsonism: Selective lesion of nigrostriatal neurons by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces an extrapyramidal syndrome in rhesus monkeys

Chiueh, Chuang C.; Burns, R. S.; Markey, Sanford P.; Jacobowitz, David M.; Kopin, Irwin J.

doi:10.1016/0024-3205(85)90061-x

Cited by 129 publications

(33 citation statements)

References 13 publications

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“…Our results confirm this variability in DAT labeling and show that neurons with the highest labeling are preferentially localized in SNCv and those with the lowest in A10. The facts that the ventrolateral to dorsomedial gradient does not change in rats, monkeys, and humans and that 6-OHDA in rat (this study), MPTP in monkey (Chiueh et al, 1985;Schneider et al, 1987;Herrero et al, 1993;Varastet et al, 1994), and PD in human (German et al, 1989;Goto et al, 1989;Fearnley and Lees, 1991;Gibb and Lees, 1991;Damier et al, 1999b) follow the same pattern of degeneration matching this gradient suggest that DAT levels are a common factor of the differential vulnerability and that they may play a pivotal role at the onset of the neurodegenerative process in PD.…”

Section: Dat and Vmat2 Expression And Vulnerability Of Midbrain Da Cellssupporting

confidence: 54%

“…In adition, its topographic pattern of degeneration has not been as precisely established as the patterns of A9 and A10. In the rat, with cytoarchitectural and neurochemical criteria (McRitchie et al, 1996;Gonzalez-Hernandez and Rodriguez, 2000) and the topographical pattern of degeneration observed in PD (Bernheimer et al, 1973;Hirsch et al, 1988;Damier et al, 1999b) and different models of PD (Chiueh et al, 1985;Schneider et al, 1987;Herrero et al, 1993;Varastet et al, 1994;Rodriguez et al, 2001b) borne in mind, A9 was divided into two subregions (Fig. 1A-C): 1) the caudoventrolateral region of the SN (SNcv), which includes A9 DA cells lying in the ventrolateral region of the SN pars compacta (SNC) and the SN pars reticulata (SNR), and 2) the rostrodorsomedial region of the SNC (SNrm), and A10 was divided into: 1) the ventral tegmental area and parabrachial pigmented nucleus (VTA/PBP), containing mediumsized and large cells lying in the paramedial ventral midbrain and above SNC, respectively, and 2) the rostral and caudal linear nuclei and interfascular nucleus (Li/IF), formed by small cells lying in and close to the midbrain midline.…”

Section: Division Of the Midbrain Da Formation For The Morphological mentioning

confidence: 97%

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Expression of dopamine and vesicular monoamine transporters and differential vulnerability of mesostriatal dopaminergic neurons

González‐Hernández

Barroso‐Chinea

Muros

et al. 2004

J of Comparative Neurology

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Numerous studies suggest that the dopamine transporter (DAT), responsible for dopamine reuptake, may act as a vulnerability factor in the pathogenesis of Parkinson's disease (PD) and the vesicular monoamine transporter (VMAT2), responsible for its vesicular storage, as a neuroprotective factor. However, the relevance of each on the differential vulnerability of midbrain DA cells remains unknown. Here we studied the relationship between the expression pattern (mRNA and protein) of both transporters and the differential vulnerability of midbrain DA cells in a model of PD (intracerebroventricular injection of 6-OHDA in rats) and in monkey and human midbrain. Our results revealed that the expression patterns for VMAT2 mRNA and protein and DAT mRNA are similar, with the highest levels in the rostromedial region of substantia nigra (SNrm), followed by the caudoventral region of SN (SNcv), the ventral tegmental area and pigmented parabrabraquial nucleus (VTA/PBP), and finally the linear and interfascicular nuclei (Li/IF). In contrast, the expression of DAT protein in rats, monkeys, and humans followed a caudoventrolateral-to-rostrodorsomedial decreasing gradient (SNcv > SNrm > VTA/PBP > Li/IF), matching the degeneration profile observed after intracerebroventricular injection of 6-OHDA and in PD. In addition, DAT blockade made all midbrain DA cells equally resistant to 6-OHDA. These data indicate that DAT protein levels, but not DAT mRNA levels, are closely related to the differential vulnerability of midbrain DA cells and that this relationship is unaffected by the relative levels of VMAT2. Furthermore, the difference between DAT mRNA and protein profiles suggests internuclear differences in its posttransductional regulation.

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Section: Dat and Vmat2 Expression And Vulnerability Of Midbrain Da Cellssupporting

confidence: 54%

Section: Division Of the Midbrain Da Formation For The Morphological mentioning

confidence: 97%

Expression of dopamine and vesicular monoamine transporters and differential vulnerability of mesostriatal dopaminergic neurons

González‐Hernández

Barroso‐Chinea

Muros

et al. 2004

J of Comparative Neurology

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“…1-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) induces extrapyramidal motor dysfunction which mimics major clinical signs of the Parkinson's disease in humans, monkeys, and mice (Davis et al, 1979;Langston et al, 1983;Burns et al, 1983;Chiueh et al, 1985;Heikkila et al, 1984;, Table 1. Interleukin-2 (IL-2) and basic fibroblast growth factor (bFGF) contents (mean -+ S.E.M.)…”

Section: Discussionmentioning

confidence: 99%

Interleukin-2 but not basic fibroblast growth factor is elevated in parkinsonian brain

Mogi

Harada

Kondo

et al. 1996

J. Neural Transmission

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The contents of interleukin (IL)-2 and basic fibroblast growth factor (bFGF) were measured in the brain (caudate nucleus, putamen, and cerebral cortex) from control and parkinsonian patients by highly sensitive enzyme-linked immunosorbent assay (ELISA). The concentrations of IL-2 in the brain were in the order of pg/mg protein, and the values were significantly higher in the caudate and putamen from parkinsonian patients than those from control patients. However, the levels of IL-2 in the cerebral cortex showed no significant difference between parkinsonian and control patients. In contrast to IL-2, the bFGF levels in the brain were high and in the order of ng/mg protein, and there was no significant difference in the caudate and putamen between parkinsonian and control patients. Although both IL-2 and bFGF may play important roles in dopaminergic neurons as neurotrophic factors, IL-2 but not bFGF may relate to the compensatory response in the nigrostriatal dopaminergic regions in parkinsonian brain during progress of neurodegeneration.

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“…MPTP-induced extrapyramidal motor dysfunction, which mimics major clinical signs of the C.J. Sun et al idiopathic Parkinson's disease, is only observed in human subjects (Davis et al, 1979;Langston et al, 1983;Burns et al, 1986) and nonhuman primates (Burns et al, 1983Langston et al, 1984;Chiueh et al, 1985a;Jenner et al, 1986). It is believed that a low dose of MPTP causes a selective destruction of the substantia nigra pars compacta neurons and produces a persistent parkinsonian syndrome only in monkeys which exhibit more than an 80% decrease in striatal dopamine (Chiueh et al, 1985a).…”

Section: Introductionmentioning

confidence: 93%

Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+

Sun

Johannessen

Gessner

et al. 1988

J. Neural Transmission

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Unilateral intranigral administration of the oxidative metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenyl-dihydropyridine (MPDP+) or 1-methyl-4-phenylpyridine (MPP+) produced dose-dependently a depletion of dopamine in the ipsilateral striatum of rats two weeks following treatment. d-Amphetamine and apomorphine induced circling toward the lesioned side in these unilaterally treated animals. No contralateral circling behavior was observed after challenging with apomorphine. This dopamine lesioning effect of MPP+ was not blocked by pretreatment of animals with a dopamine uptake blocker, GBR 12909. Furthermore, MPP+ increased the 45Ca accumulation into cells at the site of injection and produced "nonspecific" cell membrane and/or cytotoxic damage seen by histological procedures. These results indicate that MPDP+ and MPP+ produced localized cytotoxic damage to nigrostriatal neurons, caused a decrease in striatal dopamine, and disrupted the nigrostriatal system's functioning following intranigral administration to rats. It is postulated that the cationic surfactant properties of MPDP+ and MPP+ might contribute to its neurotoxic effects.

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III. Primate model of parkinsonism: Selective lesion of nigrostriatal neurons by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces an extrapyramidal syndrome in rhesus monkeys

Cited by 129 publications

References 13 publications

Expression of dopamine and vesicular monoamine transporters and differential vulnerability of mesostriatal dopaminergic neurons

Expression of dopamine and vesicular monoamine transporters and differential vulnerability of mesostriatal dopaminergic neurons

Interleukin-2 but not basic fibroblast growth factor is elevated in parkinsonian brain

Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+

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