Effect of Quercetin in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-Induced Mouse Model of Parkinson's Disease

Lv, Chuanfeng; Hong, Tie; Yang, Zhen; Zhang, Yu; Wang, Lu; Dong, Min; Zhao, Jing; Mu, Jiaye; Meng, Yixiao

doi:10.1155/2012/928643

Cited by 87 publications

(68 citation statements)

References 19 publications

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“…In this study we found that the injection of MPTP increased nigral 4-HNE amount. These findings are consistent with the literature data [52,53]. In our study, the administration of DHA decreased the content of 4-HNE in the substantia nigra of DHA+MPTP group.…”

Section: Discussionsupporting

confidence: 94%

Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Parlak

Özkan

Dilmaç

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on Parkinson's disease (PD). The aim of this study was to investigate if the DHA acts on neurons of substantia nigra (SN) by phosphorylation of neuronal nitric oxide synthase (nNOS) in an experimental mouse model of PD. Material and methods. An experimental model of PD was created by intraperitoneal injections (4 × 20 mg/kg) of the neurotoxin 1-methyl-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Three-month-old male C57BL/6 mice were randomly divided into four groups as follows: control (C), DHA-treated (DHA), MPTP-injected (MPTP) and DHA-treated and MPTP-injected (DHA + MPTP). DHA (36 mg/kg/day) was administered daily by gavage for four weeks. Motor activity of the mice was evaluated with pole, locomotor activity and rotarod tests. Caspase-3 activity, nitrate/nitrite and 4-hydroxynonenal (4-HNE) levels were determined by spectrophotometric assays. Immunohistochemistry was used to localize and assess the expressions of tyrosine hydroxylase (TH), nNOS and phospho-nNOS (p-nNOS) in SN.Results. An increased return and total down time in the MPTP group was observed in the pole test, while DHA treatment decreased both parameters. The ambulatory activity, total distance and total locomotor activities were decreased in the MPTP group, whereas they were increased by DHA treatment. MPTP-treated animals exhibited shorter time on the rod test which was significantly increased by DHA treatment. DHA administration significantly decreased 4-HNE and nitrate/nitrite levels of SN supernatants and protected the TH (+) dopaminergic neurons of SN in the DHA + MPTP group compared to the MPTP group. DHA treatment significantly decreased nNOS and increased p-nNOS immunoreactivities in the DHA + MPTP group compared to the MPTP group. Conclusions. These results indicate that DHA treatment protects dopaminergic neurons in SN via increasing nNOS serine 852 phosphorylation in the experimental mice model of PD.

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Section: Discussionsupporting

confidence: 94%

Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Parlak

Özkan

Dilmaç

et al. 2015

Folia Histochem Cytobiol.

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“…Quercetin administration to neurons attenuated 1-methyl-4-phenylpyridinium (MMP) evoked microglia activation, which is a precursor for PD pathogenesis [124]. Studies have also shown that quercetin promises neuroprotection in PD mice model by stimulating glutathione peroxidase (GPx), superoxide dismutase (SOD), Na( + ), and K( + )-ATPase [141]. Quercetin suppressed cell death in PD cell model while its metabolite quercetin-3- O - β -glucuronide, due to its low absorption, did not affect cell viability [142].…”

Section: Polyphenols and Pharmacological Propertiesmentioning

confidence: 99%

Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

Bhullar

Rupasinghe

2013

Oxidative Medicine and Cellular Longevity

350

194

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Aging leads to numerous transitions in brain physiology including synaptic dysfunction and disturbances in cognition and memory. With a few clinically relevant drugs, a substantial portion of aging population at risk for age-related neurodegenerative disorders require nutritional intervention. Dietary intake of polyphenols is known to attenuate oxidative stress and reduce the risk for related neurodegenerative diseases such as Alzheimer's disease (AD), stroke, multiple sclerosis (MS), Parkinson's disease (PD), and Huntington's disease (HD). Polyphenols exhibit strong potential to address the etiology of neurological disorders as they attenuate their complex physiology by modulating several therapeutic targets at once. Firstly, we review the advances in the therapeutic role of polyphenols in cell and animal models of AD, PD, MS, and HD and activation of drug targets for controlling pathological manifestations. Secondly, we present principle pathways in which polyphenol intake translates into therapeutic outcomes. In particular, signaling pathways like PPAR, Nrf2, STAT, HIF, and MAPK along with modulation of immune response by polyphenols are discussed. Although current polyphenol researches have limited impact on clinical practice, they have strong evidence and testable hypothesis to contribute clinical advances and drug discovery towards age-related neurological disorders.

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“…Alternatively, quercetin may induce PON2 expression by activating estrogen receptors alpha (Galluzzo et al 2009), though this would need to be investigated further. Independent of the underlying mechanism(s), the ability of quercetin to induce PON2 may play a role in the reported neuroprotective actions of this polyphenol, which have been observed in vitro (Mercer et al 2005; Ossola et al 2009; Bournival et al 2009), as well as in vivo (Barcelos et al 2011; Lv et al 2012; Selvakumar et al 2012). In striatal astrocytes from PON2 +/+ mice (mixed gender), exposure for 24 h to quercetin abolished the increase in ROS levels caused by H 2 O 2 or DMNQ, and resulted in protection against the cytotoxicity of these oxidants.…”

Section: Modulation Of Pon2mentioning

confidence: 99%

Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection

Costa¹,

Laat²,

Dao³

et al. 2014

NeuroToxicology

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Paraoxonase 2 (PON2) is a member of a gene family which also includes the more studied PON1, as well as PON3. PON2 is unique among the three PONs, as it is expressed in brain tissue. PON2 is a lactonase and displays anti-oxidant and anti-inflammatory properties. PON2 levels are highest in dopaminergic regions (e.g. striatum), are higher in astrocytes than in neurons, and are higher in brain and peripheral tissues of female mice than male mice. At the sub-cellular level, PON2 localizes primarily in mitochondria, where it scavenges superoxides. Lack of PON2 (as in PON2−/− mice), or lower levels of PON2 (as in male mice compared to females) increases susceptibility to oxidative stress-induced toxicity. Estradiol increases PON2 expression in vitro and in vivo, and provides neuroprotection against oxidative stress. Such neuroprotection is not present in CNS cells from PON2−/− mice. Similar results are also found with the polyphenol quercetin. PON2, given its cellular localization and antioxidant and anti-inflammatory actions, may represent a relevant enzyme involved in neuroprotection, and may represent a novel target for neuroprotective strategies. Its differential expression in males and females may explain gender differences in the incidence of various diseases, including neurodevelopmental, neurological, and neurodegenerative diseases.

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Effect of Quercetin in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-Induced Mouse Model of Parkinson's Disease

Cited by 87 publications

References 19 publications

Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid protects dopaminergic neurons in an experimental model of Parkinson’s disease

Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases

Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection

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