Repeated intranigral MPTP administration: A new protocol of prolonged locomotor impairment mimicking Parkinson's disease

Reksidler, Angela B.; Lima, Maurício Andrade de; Dombrowski, Patrícia A.; Andersen, Mônica Levy; Zanata, Sı́lvio M.; Andreatini, Roberto; Tufik, Sérgio; Vital, Maria A.B.F.

doi:10.1016/j.jneumeth.2007.08.024

Cited by 32 publications

(15 citation statements)

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“…This data is in agreement with a previous report that detected SNpc microglial activation 7 days post-injection of intrastriatal LPS [34]. Accordingly, the neurochemical profile promoted by LPS was comparable to that elicited by MPTP, which is considered a toxin that generates a mild neurodegeneration, even in a repeated intranigral administration protocol [12]. Hence, it is postulated that MPTP particularly model the early phase of PD, which is primarily characterized by the occurrence of cognitive, emotional and sleep deficits, than motor abnormalities [6,8,10,14,21,35].…”

Section: Discussionsupporting

confidence: 93%

“…In addition, loss of tyrosine hydroxylase immunoreactivity (TH-ir) began in axons at 6 h, and progressed to cell bodies at later time-points post lesion [36]. Similarly, MPTP can cause a short term dopaminergic neurodegeneration with reductions of nigral TH expression as well as TH-ir cell death [4,8,12]. Moreover, a single injection of LPS to the SNpc region of Wistar, Fisher or Sprague-Dawley rats indeed leads to a fast marked loss (50-85%) of SNpc dopaminergic neurons [1,38].…”

Section: Discussionmentioning

confidence: 99%

“…Some models of PD are achieved by the use of neurotoxins, in particular 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), and recently the endotoxin found in the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS) [1][2][3]. In most of the studies of PD models, several of the motor, cognitive, affective, neurochemical, inflammatory and sleep disruptions encountered in the human disease are partially recapitulated by MPTP, 6-OHDA and LPS [4][5][6][7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Intranigral LPS Administration Produces Dopamine, Glutathione but not Behavioral Impairment in Comparison to MPTP and 6-OHDA Neurotoxin Models of Parkinson’s Disease

et al. 2010

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The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) administrations, in the light of neurochemical, behavioral and endogenous antioxidant glutathione alterations. All the results were collected 1, 3 and 7 days after the lesions. LPS produced a delayed reduction of striatal dopamine, whereas homovanillic acid was drastically increased at the first time-point. Comparatively, MPTP promoted dopamine reduction 3 and 7 days with increase of homovanillic acid. Whilst, 6-OHDA generated initial increase of dopamine and homovanillic acid followed by subsequent decrease of this neurotransmitter accompanied by reductions of dopamine metabolites at the same periods. Furthermore, nigral glutathione demonstrated to be a far more sensitive target for LPS than for MPTP or 6-OHDA. Behavioral data indicated impairments induced by MPTP, 6-OHDA but not LPS. In conclusion, it is suggested that intranigral LPS can provide new insights about neuroinflammation, simulating features of the pre-motor phase of Parkinson's disease.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intranigral LPS Administration Produces Dopamine, Glutathione but not Behavioral Impairment in Comparison to MPTP and 6-OHDA Neurotoxin Models of Parkinson’s Disease

et al. 2010

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“…Considering the current results, it is proposed that the intranigral rotenone is an accurate model to induce neurochemical, histological, and cognitive-like alterations similar to PD. In addition, the histological evidence denoted a remarkable reduction of about 60% in the number of TH-ir within the SNpc, a slightly increased neuronal loss compared to MPTP Reksidler et al 2008). Moreover, we did not detect significant alterations in the number of TH-ir neurons in the ventral tegmental area (data not shown), indicating that the neurotoxin delivery occurred in a site-specific fashion, as expected.…”

Section: Discussionsupporting

confidence: 72%

“…For each rat, 12 sections of 30 lm thick were cut on a cryostat in the coronal plane covering about 360 lm (-4.92 to -5.28 from bregma) of the midbrain (Paxinos and Watson 2005). These coordinates correspond to the maximal extent of the dopaminergic neurons within the SNpc (Reksidler et al 2008;Santiago et al 2010). Tissue sections were incubated with primary antibody anti-TH, raised in rabbits, diluted in PBS containing 0.3% Triton X-100 (1:500; Chemicon, CA, USA) overnight at 4°C.…”

Section: Th Immunostainingmentioning

confidence: 99%

Behavioral, Neurochemical and Histological Alterations Promoted by Bilateral Intranigral Rotenone Administration: A New Approach for an Old Neurotoxin

et al. 2011

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Rotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy of rotenone as an animal model of Parkinson's disease (PD). In order to counteract these limitations, this study characterized a precise neurotoxin-delivery strategy employing the bilateral intranigral administration protocol of rotenone as a reliable model of PD. We performed bilateral intranigral injections of rotenone (12 μg) and subsequent general activity (1, 10, 20, and 30 days after rotenone) and cognitive (7, 8, 15, and 30 days after rotenone) evaluations followed by neurochemical and immunohistochemical tests. We have observed that rotenone was able to produce a remarkable reduction on the percentage of tyrosine hydroxylase immunoreactive neurons (about 60%) within the substantia nigra pars compacta. Dopamine (DA) was severely depleted at 30 days after rotenone administration, similarly to its metabolites. In addition, an increase in DA turnover was detected at the same time-point. In parallel, striatal serotonin and its metabolite were found to be increased 30 days after the neurotoxic insult, without apparent modification in the serotonin turnover. Besides, motor behavior was impaired, mainly 1 day after rotenone. Furthermore, learning and memory processes were severely disrupted in different time-points, particularly at the training and test session (30 days). We now provide further evidence of a time-dependent neurodegeneration associated to cognitive impairment after the single bilateral intranigral administration of rotenone. Thus, it is proposed that the current rotenone protocol provides an improvement regarding the existing rotenone models of PD.

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MicroRNA‐190 alleviates neuronal damage and inhibits neuroinflammation via Nlrp3 in MPTP‐induced Parkinson's disease mouse model

Sun

Wang

Chen

et al. 2019

Journal Cellular Physiology

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Parkinson's disease (PD) is neurodegenerative dyskinesia characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Although neuroinflammation is one of the pathological features of PD, its mechanism of promoting PD is still not fully understood. Recently, the microRNA (miR) is considered to play a critical regulatory role in inflammatory responses. In this study, we examined the antiinflammatory activity, antineuronal injury, and the underlying target of miR-190 with MPTP-induced PD mouse model and BV2 cells. The results showed that miR-190 is downregulated in lipopolysaccharide (LPS)-induced BV2 cells; however, when the miR-190 overexpressed, the expression of proinflammatory mediators, such as iNOS, IL-6, TNF-α, and TGF-β1, were inhibited and the anti-inflammatory mediator such IL-10 was increased.In addition, we predicted the potential target of miR-190 to be Nlrp3 and verified by luciferase reporter assay. The results also showed that Nlrp3 was upregulated in LPSinduced BV2 cells, whereas knockdown of Nlrp3 inhibited the LPS-induced inflammatory response in BV2 cells. Furthermore, upregulation of miR-190 or knockdown of Nlrp3 inhibited LPS-induced apoptosis in BV2 cells. However, the apoptosis inhibition effect of miR-190 was abrogated by overexpression of Nlrp3. Finally, upregulation of miR-190 inhibited the activation of microglial cells and inflammation and attenuated the tyrosine hydroxylase loss in SNpc in MPTP-induced PD mice. In conclusion, we demonstrated that miR-190 alleviates neuronal damage and inhibits inflammation via negatively regulating the expression and activation of Nlrp3 in MPTP-induced PD mouse model.

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Repeated intranigral MPTP administration: A new protocol of prolonged locomotor impairment mimicking Parkinson's disease

Cited by 32 publications

References 34 publications

Intranigral LPS Administration Produces Dopamine, Glutathione but not Behavioral Impairment in Comparison to MPTP and 6-OHDA Neurotoxin Models of Parkinson’s Disease

Intranigral LPS Administration Produces Dopamine, Glutathione but not Behavioral Impairment in Comparison to MPTP and 6-OHDA Neurotoxin Models of Parkinson’s Disease

Behavioral, Neurochemical and Histological Alterations Promoted by Bilateral Intranigral Rotenone Administration: A New Approach for an Old Neurotoxin

MicroRNA‐190 alleviates neuronal damage and inhibits neuroinflammation via Nlrp3 in MPTP‐induced Parkinson's disease mouse model

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