Excessive levels of nitric oxide in rat model of Parkinson’s disease induced by rotenone

Xiong, Zheqiang; Lang, Jessica; Xu, Gang; Li, Haiyu; Zhang, Yun; Wang, Lei; Su, Yao; Sun, Aihua

doi:10.3892/etm.2014.2099

Cited by 42 publications

(34 citation statements)

References 48 publications

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“…Similar results have also been reported by some earlier studies (Xiong et al, 2015). This weight loss could be due to the reduced food intake, disturbance in gastric motility and stool frequency (Xiong et al).…”

Section: Discussionsupporting

confidence: 90%

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Ahmed¹,

Shaikh²,

Baloch³

et al. 2018

Int. J. Morphol.

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SUMMARY:Among the neurodegenerative disorders, Parkinson disease (PD) is ranked as second most common. The pathological hallmark is selective degeneration of the dopaminergic neurons in the nigro-striatal regions of brain with appearance of the Lewy bodies. Present study explores the neuro-protective potential of polydatin in terms of amelioration of degeneration of dopaminergic neurons in nigro-striatal regions of brain and distorted neuromotor behavior in the rotenone model of Parkinson's disease. Thirty-six male Sprague Dawley rats were divided into three groups. Group A (control), Group B (rotenone treated) and Group C (rotenone+polydatin treated). Rotenone was administrated intraperitoneally (i.p) at a dose of 3 mg/kg/body weight while polydatin was given i.p. at a dose of 50 mg/ kg/body weight for four weeks. Then, animals were sacrificed; substantia nigra (SN) & striatum isolated from brain and five micron thick sections were prepared. Cresyl violet (CV), H&E and Immuno-histochemical staining using anti-TH antibody was done. Motor behavior was assessed weekly throughout the experiment using five different methods. Rotenone treated parkinsonian animals showed deterioration of motor behavior, weight loss, loss of dopaminergic neurons and diminished immune-reactivity in the sections from the nigrostriatal regions of these animals Polydatin+rotenone treatment showed contradicting effects to parkinsonism, with amelioration in weight loss, neuro-motor behavior, dopaminergic loss and immune-reactivity against dopaminergic neurons. Present study revealed a neuro-protective potential of polydatin in animal model of PD by ameliorating the neuro-motor abnormalities and degeneration of dopaminergic neurons in nigrostriatal regions.

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Section: Discussionsupporting

confidence: 90%

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Ahmed¹,

Shaikh²,

Baloch³

et al. 2018

Int. J. Morphol.

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“…In accord with our findings in human neurons, prior studies in rodents have suggested that aberrant expression of a-syn increases the vulnerability of SNpc neurons to the neurotoxic effects of PQ/MB or Rot (55,56). In rodents, treatment with PQ/MB or Rot causes degeneration of SNpc neurons and locomotor deficits consistent with a Parkinsonian phenotype (57)(58)(59)(60). PQ and Rot are believed to inhibit mitochondrial complex I (8,13,61), whereas MB is reported to inhibit mitochondrial complex I and III, increasing oxidative stress (62,63).…”

Section: Discussionsupporting

confidence: 90%

Nitration of microtubules blocks axonal mitochondrial transport in a human pluripotent stem cell model of Parkinson's disease

Stykel¹,

Humphries²,

Kirby³

et al. 2018

FASEB j.

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Neuronal loss in Parkinson's disease (PD) is associated with aberrant mitochondrial function in dopaminergic (DA) neurons of the substantia nigra pars compacta. An association has been reported between PD onset and exposure to mitochondrial toxins, including the agrochemicals paraquat (PQ), maneb (MB), and rotenone (Rot). Here, with the use of a patient-derived stem cell model of PD, allowing comparison of DA neurons harboring a mutation in the α-synuclein (α-syn) gene ( SNCA-A53T) against isogenic, mutation-corrected controls, we describe a novel mechanism whereby NO, generated from SNCA-A53T mutant neurons exposed to Rot or PQ/MB, inhibits anterograde mitochondrial transport through nitration of α-tubulin (α-Tub). Nitration of α-Tub inhibited the association of both α-syn and the mitochondrial motor protein kinesin 5B with the microtubules, arresting anterograde transport. This was, in part, a result of nitration of α-Tub in the C-terminal domain. These effects were rescued by inhibiting NO synthesis with the NOS inhibitor Nω-nitro-L-arginine methyl ester. Collectively, our results are the first to demonstrate a gene by environment interaction in PD, whereby agrochemical exposure selectively triggers a deficit in mitochondrial transport by nitrating the microtubules in neurons harboring the SNCA-A53T mutation.-Stykel, M. G., Humphries, K., Kirby, M. P., Czaniecki, C., Wang, T., Ryan, T., Bamm, V., Ryan, S. D. Nitration of microtubules blocks axonal mitochondrial transport in a human pluripotent stem cell model of Parkinson's disease.

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“…It is a neurotransmitter in the basal ganglia of the central nervous system (CNS), and it is known that its synthesis increases in PD [39]. Previous studies have shown that the activity of iNOS and nNOS, which plays a role in the synthesis of NO, also has a role in the developing of neurodegeneration in PD [40].…”

Section: Discussionmentioning

confidence: 99%

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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Excessive levels of nitric oxide in rat model of Parkinson’s disease induced by rotenone

Cited by 42 publications

References 48 publications

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Neuroprotective Potential of Polydatin Against Motor Abnormalities and Dopaminergic Neuronal Loss in Rotenone Induced Parkinson Model

Nitration of microtubules blocks axonal mitochondrial transport in a human pluripotent stem cell 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

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