Elevation Of Striatal Interleukin‐6 and Serum Corticosterone Contents In Mptp‐Treated Mice

Kaku, Koichi; Shikimi, Todahiro; Kamisaki, Yoshínori; Shinozuka, Kazumasa; Ishino, Hiroshi; Okunishi, Hideki; Takaori, Shuji

doi:10.1046/j.1440-1681.1999.03113.x

Cited by 20 publications

(11 citation statements)

References 35 publications

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“…Genetic ablation of either Tnf-α or both its receptors, Tnfrsf1 and Tnfrsf2 is reported to confer protection against MPTP toxicity as measured by attenuation of dopamine depletion in the striatum (Sriram et al, 2002,Ferger et al, 2004,Sriram et al, 2006a,Sriram et al, 2006b, although neither genetic ablation nor pharmacological manipulation of Tnf-α prevents neuronal loss in the SNpc (Rousselet et al, 2002,Ferger et al, 2004,Leng et al, 2005. Therefore, our results are consistent with the view that although Tnf-α may influence dopaminergic terminals in the striatum, it cannot explain genetic resistance to MPTP as measured by loss of TH-positive neurons in the SNpc.Our results for Il-6 mRNA levels also support prior studies showing that MPTP increases striatal Il-6 levels (Kaku et al, 1999,Hebert et al, 2003. Additionally, we show that MPTP elicits higher levels of Il-6 mRNA in SWR compared to C57BL/6J mice, suggesting that this cytokine may contribute to MPTP resistance.…”

supporting

confidence: 90%

“…Differences between strains were analyzed by two-way ANOVA followed by Bonferroni's post-test. Prior studies have reported increases in Tnf-α and Il-6 using the MPTP model (Kaku et al, 1999,Hebert et al, 2003, and mice deficient in Tnf-α receptors or Il-6 have altered responsiveness to MPTP (Bolin et al, 2002,Sriram et al, 2002,Cardenas and Bolin, 2003,Ferger et al, 2004,Leng et al, 2005. Therefore, we examined levels of Tnf-α and Il-6 mRNA in both sensitive and resistant strains of mice.…”

mentioning

confidence: 99%

“…A more telling experiment will be to assess whether loss of Mcp-1/Ccl2 causes the normally resistant SWR strain to become sensitive. Finally, though the acute model of MPTP (4 X 20 mg/kg) is widely used (Jackson-Lewis et al, 1995,Hamre et al, 1999,Kaku et al, 1999,Schwarting et al, 1999,Araki et al, 2001,Bolin et al, 2002,Rousselet et al, 2002,Cook et al, 2003,Ferger et al, 2004,Faherty et al, 2005, inflammation could potentially have a different role when animals are chronically treated with this neurotoxicant. Indeed, MPTP dosage and its injection schedule are important determinants of the mode of neurodegeneration in the SNpc (Sonsalla and Heikkila, 1986,Jackson-Lewis et al, 1995,Eberhardt and Schulz, 2003,Youdim and Arraf, 2004,Novikova et al, 2006.…”

mentioning

confidence: 99%

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Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

2007

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). With the exception of a few rare familial forms of the disease, the precise molecular mechanisms underlying PD are unknown. Inflammation is a common finding in the PD brain, but due to the limitation of postmortem analysis its relationship to disease progression cannot be established. However, studies using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have also identified inflammatory responses in the nigrostriatal pathway that precede neuronal degeneration in the SNpc. To assess the pathological relevance of these inflammatory responses and to identify candidate genes that might contribute to neuronal vulnerability, we used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to measure mRNA levels of 11 cytokine and chemokine encoding genes in the striatum of MPTP-sensitive (C57BL/6J) and MPTP-insensitive (Swiss Webster, SWR) mice following administration of MPTP. The mRNA levels of all 11 genes changed following MPTP treatment, indicating the presence of inflammatory responses in both strains. Furthermore, of the 11 genes examined only 3, interleukin 6 (Il-6), macrophage inflammatory protein 1 alpha/CC chemokine ligand 3 (Mip-1alpha/Ccl3) and macrophage inflammatory protein 1 beta/CC chemokine ligand 4 (Mip-1beta/Ccl4), were differentially regulated between C57BL/6J and SWR mice. In both mouse strains, the level of monocyte chemoattractant protein 1/CC chemokine ligand 2 (Mcp-1/Ccl2) mRNA was the first to increase following MPTP administration, and might represent a key initiating component of the inflammatory response. Using Mcp-1/Ccl2 knockout mice backcrossed onto a C57BL/6J background we found that MPTP-stimulated Mip-1alpha/Ccl3 and Mip-1beta/Ccl4 mRNA expression was significantly lower in the knockout mice; suggesting that Mcp-1/Ccl2 contributes to MPTP-enhanced expression of Mip-1alpha/Ccl3 and Mip-1beta/Ccl4. However, stereological analysis of SNpc neuronal loss in Mcp-1/Ccl2 knockout and wild-type mice showed no differences. These findings suggest that it is the ability of dopaminergic SNpc neurons to survive an inflammatory insult, rather than genetically determined differences in the inflammatory response itself, that underlie the molecular basis of MPTP resistance.

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supporting

confidence: 90%

mentioning

confidence: 99%

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confidence: 99%

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Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

2007

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“…This occurs early in neuronal degeneration, starting at the extending fibres, such as the dendrite which extends into the SN reticulata (Sugama et al, 2003). Hence, activated glial cells release detrimental compounds such as, interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ), which may act by stimulating inducible nitric oxide synthase (iNOS), or which may exert a more direct deleterious effect on DAergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis (Kataoka et al, 1997;Mogi et al, 1998;Kaku et al, 1999;KurkowskaJastrzębska et al, 1999a,b;Knott et al, 2000;Iravani et al, 2002;Teismann et al, 2003;Przybyłkowski et al, 2004;de Meira Santos Lima et al, 2006). Microglia can also induce neuritic beading (Takeuchi et al, 2005) or synaptic stripping along dendrites (Schiefer et al, 1999) leading to synaptic disconnection and loss of trophic support and cell death (Isacson et al, 1985;Jiang et al, 2006).…”

Section: Studymentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Esposito

Matteo

Benigno

et al. 2007

Experimental Neurology

218

176

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Parkinson's disease (PD) is known to be a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of experimental evidence indicates that the factors involved in the pathogenesis of this disease are several, occurring inside and outside the DAergic neuron. Recently, the role of the neuron-glia interaction and the inflammatory process, in particular, has been the object of intense study by the research community. It seems to represent a new therapeutic approach opportunity for this neurological disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-2) is upregulated in SNc DAergic neurons in both PD patients and animal models of PD and, furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) pre-treatment protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 hydroxydopamine (6-OHDA)-induced nigrostriatal dopamine degeneration. Moreover, recent epidemiological studies have revealed that the risk of developing PD is reduced in humans who make therapeutical use of NSAIDs. Consequently, it is hypothesized that they might delay or prevent the onset of PD. However, whether or not these common drugs may also be of benefit to those individuals who already have Parkinson's disease has not as yet been shown.In this paper, evidence relating to the protective effects of aspirin or other NSAIDs on DAergic neurons in animal models of Parkinson's disease will be discussed. In addition, the pharmacological mechanisms by which these molecules can exert their neuroprotective effects will be reviewed. Finally, epidemiological data exploring the effectiveness of NSAIDs in the prevention of PD and their possible use as adjuvants in the therapy of this neurodegenerative disease will also be examined.

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“…In the MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model of PD, inflammatory reactions have been determined [9][10][11] and elevated pro-inflammatory cytokines have been found [12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Targeting of cell death and neuroinflammation with peptide-linked iron oxide nanoparticles and Gd-DTPA in a mouse model of Parkinson's disease

Sclavons

Boutry²,

Laurent

et al. 2015

JBEI

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Parkinson's disease (PD) is one of the most common neurodegenerative disease and remains difficult to diagnose by conventional methods of early detection. It is characterized by the apoptotic loss of dopaminergic neurons (DN) and a neuroinflammation mainly located in the ventral midbrain (VM).The aim of this work is to study new vectorized contrast agents for magnetic resonance imaging (MRI) detection of PD injured areas by targeting apoptosis and inflammation. Two peptides selected by phage display were used for the experiments: R826 peptide, selected for its affinity for the phosphatidylserine (PS) exposed at the external surface of apoptotic cells, and 2C peptide, selected for its affinity for TNF-α (tumor necrosis factor alpha), one of the most abundant cytokines secreted during inflammation. These peptides were grafted to pegylated iron oxide nanoparticles (PEG-USPIO) and gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) for in vitro and in vivo studies, respectively. PD was simulated on mice with the MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) neurotoxin and its active metabolite MPP + (1-methyl-4-phenylpyridinium) for in vitro studies.The results showed that PEG-USPIO-R826 and PEG-USPIO-2C enabled the detection of apoptosis and inflammation, respectively, on MPP + -treated culture cells. PEG-USPIO-2C also allowed detection of inflammation on histological brain sections of MPTP-treated mice. The 2C peptide grafted to Gd-DTPA showed encouraging results in MRI detection of injured brain areas in MPTP-treated mice. These observations suggest that a targeting of damaged cells and injured areas by these new specific contrast agents occurs, offering a new tool for early diagnosis of neurodegenerative disorders like PD by MRI.

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Elevation Of Striatal Interleukin‐6 and Serum Corticosterone Contents In Mptp‐Treated Mice

Cited by 20 publications

References 35 publications

Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

Non-steroidal anti-inflammatory drugs in Parkinson's disease

Targeting of cell death and neuroinflammation with peptide-linked iron oxide nanoparticles and Gd-DTPA in a mouse model of Parkinson's disease

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