The dynamics of nigrostriatal system damage and neurobehavioral changes in the rotenone rat model of Parkinson’s disease

Troshev, Dmitry; Berezhnoy, D. S.; Kulikova, O. I.; Абаимов, Д. А.; Muzychuk, O. A.; Налобин, Д. С.; Stvolinsky, S. L.; Федорова, Т. Н.

doi:10.1016/j.brainresbull.2021.04.006

Cited by 12 publications

(10 citation statements)

References 57 publications

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“…Figure 2 shows the mechanisms of rotenone action that cause neuropathological signs, as well as motor and non-motor symptoms. It has been proven that rotenone reproduces the most common symptoms of Parkinson’s disease due to direct inhibition of the mitochondrial respiratory chain complex I [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction

Aleksandrova

Chaprov

Podturkina

et al. 2023

IJMS

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Parkinson’s disease is the second most common neurodegenerative disease. Unfortunately, there is still no definitive disease-modifying therapy. In our work, the antiparkinsonian potential of trans-epoxide (1S,2S,3R,4S,6R)-1-methyl-4-(prop-1-en-2-yl)-7-oxabicyclo [4.1.0]heptan-2,3-diol (E-diol) was analyzed in a rotenone-induced neurotoxicity model using in vitro, in vivo and ex vivo approaches. It was conducted as part of the study of the mitoprotective properties of the compound. E-diol has been shown to have cytoprotective properties in the SH-SY5Y cell line exposed to rotenone, which is associated with its ability to prevent the loss of mitochondrial membrane potential and restore the oxygen consumption rate after inhibition of the complex I function. Under the conditions of rotenone modeling of Parkinson’s disease in vivo, treatment with E-diol led to the leveling of both motor and non-motor disorders. The post-mortem analysis of brain samples from these animals demonstrated the ability of E-diol to prevent the loss of dopaminergic neurons. Moreover, that substance restored functioning of the mitochondrial respiratory chain complexes and significantly reduced the production of reactive oxygen species, preventing oxidative damage. Thus, E-diol can be considered as a new potential agent for the treatment of Parkinson’s disease.

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Section: Introductionmentioning

confidence: 99%

Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction

Aleksandrova

Chaprov

Podturkina

et al. 2023

IJMS

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“…The decrease in the sucrose preference, usually interpreted as anhedonia, is in line with this proposition [ 29 ]. It is known that toxins such as 6−OHDA, MPTP and rotenone are able to induce depressive-like behavior in rats [ 36 ] and we have previously shown the same disruption of learning in the shuttlebox in rats on the prodromal stage of rotenone-induced pathology [ 28 ]. To our knowledge, this is the first study to demonstrate this effect in C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 97%

“…In this investigation, an original method of operant learning used in our previous study with rats [ 28 ] was adapted for mice. Mice feeding behavior was registered in a plexiglass shuttlebox with a smooth black surface, consisting of two identical 25 × 25 × 30 cm compartments equipped with two automatic feeders for rationed food release (one per compartment).…”

Section: Methodsmentioning

confidence: 99%

Time Course of Neurobehavioral Disruptions and Regional Brain Metabolism Changes in the Rotenone Mice Model of Parkinson’s Disease

et al. 2022

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Parkinson’s disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3–4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats.

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“…Parkinson’s disease (PD) is a common neurodegenerative disease of the central nervous system in which the selective loss of dopamine (DA) neurons in the substantia nigra leads to the exhaustion of DA released from the nerve endings of the striatum [ 1 , 2 ], which causes clinical motor symptoms that mainly manifest as resting tremors, muscle stiffness, and slow movement [ 3 , 4 ]. Moreover, PD is accompanied by nonmotor symptoms, such as hypoosmia, gastrointestinal dysfunction, cardiovascular dysfunction, sleep disturbance and neurocognitive dysfunction [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Safranal exerts a neuroprotective effect on Parkinson’s disease with suppression of NLRP3 inflammation activation

Yang,

Wei,

Sun

et al. 2024

Mol Biol Rep

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Background Parkinson’s disease (PD) is a common central nervous system neurodegenerative disease. Neuroinflammation is one of the significant neuropathological hallmarks. As a traditional Chinese medicine, Safranal exerts anti-inflammatory effects in various diseases, however, whether it plays a similar effect on PD is still unclear. The study was to investigate the effects and mechanism of Safranal on PD. Methods The PD mouse model was established by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP firstly. Next, the degree of muscle stiffness, neuromuscular function, motor retardation and motor coordination ability were examined by observing and testing mouse movement behavior. Immunofluorescence staining was used to observe the expression of tyrosine hydroxylase (TH). The dopamine (DA) content of the striatum was detected by High-performance liquid chromatography (HPLC). The expression of TH and NLRP3 inflammasome-related markers NLRP3, IL-1β, and Capase-1 were detected by Real-time Polymerase Chain Reaction (qRT-PCR) and western blotting (WB) respectively. Results Through behavioral testing, Parkinson’s mouse showed a higher muscle stiffness and neuromuscular tension, a more motor retardation and activity disorders, together with a worse motor coordination compared with sham group. Simultaneously, DA content and TH expression in the striatum were decreased. However, after using Safranal treatment, the above pathological symptoms of Parkinson’s mouse all improved compared with Safranal untreated group, the DA content and TH expression were also increased to varying degrees. Surprisingly, it observed a suppression of NLRP3 inflammation in the striatum of Parkinson’s mouse. Conclusions Safranal played a neuroprotective effect on the Parkinson’s disease and its mechanism was related to the inhibition of NLRP3 inflammasome activation.

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The dynamics of nigrostriatal system damage and neurobehavioral changes in the rotenone rat model of Parkinson’s disease

Cited by 12 publications

References 57 publications

Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction

Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction

Time Course of Neurobehavioral Disruptions and Regional Brain Metabolism Changes in the Rotenone Mice Model of Parkinson’s Disease

Safranal exerts a neuroprotective effect on Parkinson’s disease with suppression of NLRP3 inflammation activation

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