The inflammatory response in the MPTP model of Parkinson’s disease is mediated by brain angiotensin: relevance to progression of the disease

Joglar, Belen; Rodríguez‐Pallares, Jannette; Rodríguez‐Pérez, Ana I.; Rey, Pablo; Guerra, María J.; Labandeira‐Garcia, Jose L.

doi:10.1111/j.1471-4159.2009.05999.x

Cited by 166 publications

(185 citation statements)

References 45 publications

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“…Experimental data also support the involvement of brain RAS in dopaminergic degeneration [110,111,112]. It was demonstrated that AII increased the neurotoxic effect induced by low doses of 6-OHDA, and the treatment with inhibitors of ACE [113,114,112] or blockage of AT1Rs [98,95,96] resulted in a significant reduction of both the loss of dopaminergic neurons and the levels of protein oxidation and lipid peroxidation induced by the neurotoxins [115]. Furthermore antagonist of AT1Rs has been shown to be neuroprotective [116].…”

Section: Renin-angiotensin Systemmentioning

confidence: 79%

“…The components involved in the effects of AII in peripheral tissues such as NADPH-oxidase have also been found in neurons [91] and glial cells [92,93]. It has been demonstrated the presence of different cytoplasmic and membrane subunits of the NADPH complex in mesencephalic DAergic neurons, astrocytes and microglia [94,95,96]. NADPH-oxidase complex is the most significant source of ROS other that mitochondria [97].…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

“…NADPH-oxidase complex is the most significant source of ROS other that mitochondria [97]. As a matter of fact, the neuronal loss is reduced by inhibitors of NADPH-oxidase, which suggests that NADPH activation and NADPH-derived ROS are involved in the AII-enhanced DAergic neuronal death [98,95,96]. Impaired RAS has been reported especially in aging diseases [99].…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

“…For example, several studies have reported the presence of RAS components in the basal ganglia, particularly in the nigro-striatal system [100,101,102,103]. The AT1Rs and AT2Rs were found to be expressed in primary mesencephalic cell cultures [104,95,96], in nigral DAergic neurons and glial cells in both rodents and primates [105] and it was shown that AII induces DA release, which is blocked by AT1Rs antagonists [106]. The interaction between the RAS and the DAergic system is particularly interesting, previous evidences suggested that DA and angiotensin systems directly counter-regulate each other in renal cells [107] and that abnormal counter-regulatory interactions between dopamine and AII play an important role in renal degeneration and hypertension [108].…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

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Dopamine Receptors and Neurodegeneration

Rangel‐Barajas¹,

Coronel²,

Florán³

2015

Aging and disease

191

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Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson's disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases.

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Section: Renin-angiotensin Systemmentioning

confidence: 79%

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Section: Renin-angiotensin Systemmentioning

confidence: 99%

See 2 more Smart Citations

Dopamine Receptors and Neurodegeneration

Rangel‐Barajas¹,

Coronel²,

Florán³

2015

Aging and disease

191

View full text Add to dashboard Cite

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“…In the present study, we show that morin attenuated MPP + -induced loss of cell viability and apoptosis in PC12 cells, suggesting that morin is a potential therapeutic molecule for the treatment of neurodegenerative diseases. MPP + has been shown to induce oxidative stress in vitro and in vivo [25][26][27] . In agreement with its antioxidant activity [24,28] , morin attenuated ROS formation.…”

Section: Discussionmentioning

confidence: 99%

Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo

et al. 2010

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Aim: To investigate the neuroprotective effects of morin on 1-methyl-4-phenylpyridinium ion (MPP + )-induced apoptosis in neuronal differentiated PC12 cells as well as in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease (PD). Methods: PC12 cells were challenged with MPP + in the presence or absence of morin. Cell viability was determined using MTT assay. Cell apoptosis was measured using flow cytometry. Generation of reactive oxygen species (ROS) was assayed using fluorescence assay. In an MPTP mouse model of PD, behavioral deficits, striatal dopamine content, and number of dopaminergic neurons were measured. Results: MPP + induced apoptosis and ROS formation in PC12 cells. Concomitant treatment with morin (5-50 μmol/L) significantly attenuated the loss of cell viability and apoptosis when compared with MPP + treatment alone. Morin also attenuated ROS formation induced by MPP + . MPTP induced permanent behavioral deficits and nigrostriatal lesions in mice. When administered prior to MPTP, morin (20 to 100 mg/kg) attenuated behavioral deficits, dopaminergic neuronal death and striatal dopamine depletion in the MPTP mouse model. Conclusion: The findings suggest that morin has neuroprotective actions both in vitro and in vivo, and may provide a novel therapeutic agent for the treatment of PD and other neurodegenerative diseases.

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Microglial TNF‐α mediates enhancement of dopaminergic degeneration by brain angiotensin

Borrajo

Rodríguez‐Pérez

Díaz-Ruiz

et al. 2013

Glia

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In vitro and in vivo models of Parkinson's disease were used to investigate whether TNF-α plays a major role in the enhancement of the microglial response and dopaminergic degeneration induced by brain angiotensin hyperactivity. Treatment of primary mesencephalic cultures with low doses of the neurotoxin MPP(+) induced a significant loss of dopaminergic neurons, which was enhanced by cotreatment with angiotensin II and inhibited by TNF-α inhibitors. Treatment of primary cultures with angiotensin induced a marked increase in levels of TNF-α, which was inhibited by treatment with angiotensin type-1-receptor antagonists, NADPH-oxidase inhibitors and NFK-β inhibitors. However, TNF-α levels were not significantly affected by treatment with angiotensin in the absence of microglia. The microglial origin of the angiotensin-induced increase in TNF-α levels was confirmed using dopaminergic (MES 23.5) and microglial (N9) cell lines. Inhibition of the microglial Rho-kinase activity also blocked the AII-induced increase in TNF-α levels. Treatment of the dopaminergic cell line with TNF-α revealed that NFK-β activation mediates the deleterious effect of microglial TNF-α on dopaminergic neurons. Treatment of mice with MPTP also induced significant increases in striatal and nigral TNF-α levels, which were inhibited by angiotensin type-1-receptor antagonists or NFK-β inhibitors. The present results show that microglial TNF-α plays a major role in angiotensin-induced dopaminergic cell death and that the microglial release of TNF-α is mediated by activation of angiotensin type-1 receptors, NADPH-oxidase, Rho-kinase and NFK-β.

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The inflammatory response in the MPTP model of Parkinson’s disease is mediated by brain angiotensin: relevance to progression of the disease

Cited by 166 publications

References 45 publications

Dopamine Receptors and Neurodegeneration

Dopamine Receptors and Neurodegeneration

Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo

Microglial TNF‐α mediates enhancement of dopaminergic degeneration by brain angiotensin

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