Dopamine Cell Degeneration Induced by Intraventricular Administration of 6-Hydroxydopamine in the Rat: Similarities with Cell Loss in Parkinson's Disease

Rodrı́guez, Manuel; Barroso‐Chinea, Pedro; Abdala, Patricio; Obeso, José A.; González‐Hernández, Tomás

doi:10.1006/exnr.2000.7624

Cited by 106 publications

(85 citation statements)

References 115 publications

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“…3C, G). Similar to the previous reports, 21,22) these observations demonstrate that a 6-OHDA injection to the cerebral lateral ventricle induces the damage of dopaminergic nerve terminals in the striatum and the degeneration of nerve cell bodies in the SN (Figs. 3C, G).…”

Section: Resultssupporting

confidence: 91%

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Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

Pyo

Jeong

Yeo

et al. 2013

Biological & Pharmaceutical Bulletin

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The anti-inflammatory and neuroprotective effects of trans-cinnamaldehyde (TCA) were investigated on the inflammatory cells and the dopaminergic degeneration in mice. TCA inhibited the up-regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-induced inflammatory BV2 microglial cells. To investigate the TCA efficacy on the 6-hydroxydopamine (6-OHDA)-induced dopaminergic degeneration in mice, an intracerebroventricular injection of 6-OHDA was given to the mice, and TCA (30 mg/kg) was intraperitoneally administered. At 7 d after the 6-OHDA injection, 6-OHDA led to a severe loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the striatum and substantia nigra (SN). On the other hand, TCA dramatically maintained the number of TH-positive dopaminergic neurons in the striatum and SN regions of the 6-OHDA-treated mice, which indicates that TCA is able to inhibit the 6-OHDA-induced reduction of TH expression in the dopaminergic neurons in the striatum and SN regions. TCA also inhibited the induction of iNOS and COX-2 in the 6-OHDA model, similarly as shown in the LPS-induced inflammatory BV2 microglial cells. These results indicate that TCA has a neuroprotective effect on dopaminergic neurons and that this effect may be associated with the inhibition of inflammatory responses. These findings suggest that TCA may be a therapeutic candidate for the prevention of inflammationmediated neurodegenerative diseases.

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Section: Resultssupporting

confidence: 91%

“…19,20) 6-OHDA causes nigrostriatal DA neuronal degeneration when it is directly injected into the medial forebrain bundle, striatum or SN. 21,22) The i.c.v. injection of 6-OHDA induces a dopaminergic dysfunction in mice as well.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

Pyo

Jeong

Yeo

et al. 2013

Biological & Pharmaceutical Bulletin

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“…The findings that upwards of 85% of the ER␤-IR mesostriatally projecting neurons identified in this study also contained CB-IR, a marker for midbrain DA neurons that in rats and primates are resistant to MPTP (Lavoie and Parent, 1991;Rodriguez et al, 2001), and that in humans are spared in Parkinson's disease (German et al, 1989;Yamada et al, 1990;Damier et al, 1999) add to this argument.…”

Section: Functional Roles For Identified Er␤-and Ar-ir Pathwayssupporting

confidence: 50%

Mesostriatal and mesolimbic projections of midbrain neurons immunoreactive for estrogen receptor beta or androgen receptors in rats

Creutz

Kritzer

2004

J of Comparative Neurology

121

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The dopamine (DA) inputs to the caudate putamen, the nucleus accumbens, and the amygdala in rats are sensitive to circulating estrogens and androgens. One mechanism for the hormone modulation of these systems may be via actions at cognate intracellular estrogen and androgen receptors. However, although it is known that specific subsets of midbrain DA neurons are immunopositive for estrogen receptor beta (ERbeta) or androgen receptors (ARs), it is not known where these receptor-bearing cells project. To address this issue, we combined double-label immunocytochemistry with retrograde tract tracing to identify the forebrain projections of ERbeta- or AR-immunoreactive (IR) midbrain neurons. Specifically, Fluoro-Gold and/or cholera toxin were injected into discrete subregions of the caudate-putamen, the nucleus accumbens, or the amygdala. Evaluations of the resultant midbrain labeling revealed that ERbeta-IR neurons sent collateral projections mainly to both the ventral caudate-putamen and the amygdala, but not to the dorsal caudate or nucleus accumbens. In contrast, AR-IR neurons projected either to the amygdala or the nucleus accumbens but not to the caudate-putamen. The organization of these forebrain projections concurs with some of the known hormone sensitivities of mesostriatal and mesolimbic DA systems in rats and provides an anatomical model that predicts separate influences for androgens and estrogens over mesostriatal and mesolimbic DA systems.

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“…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%

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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Dopamine Cell Degeneration Induced by Intraventricular Administration of 6-Hydroxydopamine in the Rat: Similarities with Cell Loss in Parkinson's Disease

Cited by 106 publications

References 115 publications

Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

Mesostriatal and mesolimbic projections of midbrain neurons immunoreactive for estrogen receptor beta or androgen receptors in rats

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

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