Comprehensive Perspectives on Experimental Models for Parkinson’s Disease

Ke, Minjing; Chong, Cheong-Meng; Zhu, Qi; Zhang, Ke; Cai, Cui-Zan; Lu, Jiahong; Qin, Dajiang; Su, Huanxing

doi:10.14336/ad.2020.0331

Cited by 22 publications

(10 citation statements)

References 248 publications

(261 reference statements)

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“…In terms of PD, the mapping of the zebrafish dopaminergic neural system is well established, making it an ideal model for studying the mechanisms affecting the development of PD [ 10 ]. Moreover, the advances of translational research have enabled the establishment of transgenic and neurotoxin-induced zebrafish models capable of causing PD-like symptoms in zebrafish, both genetically and phenotypically [ 2 , 11 ]. With this regard, behavioural abnormalities, neurotoxic effects, expressions of associated PD genes and proteins, immunomodulation, and many other topics have all been studied using zebrafish as a PD model.…”

Section: Introductionmentioning

confidence: 99%

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study

et al. 2022

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Parkinson’s disease (PD) is the most common brain motor disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Motor impairments, such as dyskinesia, bradykinesia, and resting tremors, are the hallmarks of PD. Despite ongoing research, the exact PD pathogenesis remains elusive due to the disease intricacy and difficulty in conducting human studies. Zebrafish (Danio rerio) has emerged as an ideal model for researching PD pathophysiology. Even though 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used to induce PD in zebrafish, behavioural findings are frequently limited to a single time point (24 hours post-injection). In this sense, we aim to demonstrate the effects of MPTP on zebrafish swimming behaviour at multiple time points. We administered a single dosage of MPTP (200μg/g bw) via intraperitoneal injection (i/p) and assessed the locomotor activity and swimming pattern at 0h, 24h, and 96h post-injection through an open field test. Analysis of the behaviour revealed significant reductions in swimming velocity (cm/s) and distance travelled (cm), concurrent with an increase in freezing maintenance (duration and bouts) in zebrafish injected with MPTP. In addition, the MPTP-injected zebrafish exhibited complex swimming patterns, as measured by the turn angle, meander, and angular velocity, and showed abnormal swimming phenotypes, including freezing, looping, and erratic movement. To conclude, MPTP administration into adult zebrafish induced hypolocomotion and elicited motor incoordination. Plus, the effects of MPTP were observable 24 hours after the injection and still detectable 96 hours later. These findings contribute to the understanding of MPTP effects on adult zebrafish, particularly in terms of swimming behaviours, and may pave the way for a better understanding of the establishment of PD animal models in the future.

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Section: Introductionmentioning

confidence: 99%

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study

et al. 2022

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“…In addition to the protective effect on ischemic tissue injury, studies have shown that RIC has a neuroprotective ( 50 ) and therapeutic effect on sleep ( 27 ). Animal studies have found that RIC can rescue approximately half of the functional dopaminergic neurons in the substantia nigra pars compacta damaged by Parkinson's neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ( 28 , 51 ). RIC has been shown to promote the survival of retinal ganglion cells after various injuries, which plays a large role in the EDS of Parkinson's disease ( 29 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of remote ischemic conditioning on sleep complaints in Parkinson's disease–rationale, design, and protocol for a randomized controlled study

Wang

Zhao

et al. 2022

Front. Neurol.

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ObjectiveSleep disturbances are common non-motor symptoms of Parkinson's disease. The symptoms affect the quality of patients' life by impeding normal sleep cycles and causing excessive daytime sleepiness. Remote Ischemic Conditioning (RIC) is a therapy often used for ischemic stroke patients to minimize infarct size and maximize post-stroke neurological function. Animal experiments have shown that RIC plays a protective role for retinal ganglion cells and other critical areas of the brain of Parkinson's disease. However, whether RIC improves excessive daytime sleepiness (EDS) for patients with Parkinson's disease remains to be determined.MethodsThis is a single-center, double-blind, and randomized controlled trial, which includes patients with Parkinson's disease with EDS. All recruited patients will be randomly assigned either to the RIC or the control group (i.e., sham-RIC) with 20 patients in each group. Both groups receive RIC or sham-RIC treatment once a day for 28 days within 24 h of enrollment. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Parkinson Disease Sleep Scale-2 (PDSS-2), Parkinson's Disease Questionnaire39 (PDQ39) score scales, and adverse events, such as inability to tolerate the treatment leading to suspension of the study or objective signs of tissue or neurovascular injury caused by RIC and/or sham-RIC are evaluated at 7, 14, 28, and 90 days after enrollment.ResultsThe primary goal of this study is to assess the feasibility of the treatments in patients with Parkinson's disease by measuring serious RIC-related adverse events and any reduced incidence of adverse events during the trial and to study potential efficacy, improvement of patients' excessive daytime sleepiness, quality of life-based on ESS, PSQI, PDSS-2, and PDQ39 scores. The secondary goal is to confirm the safety of the treatments.ConclusionThis study is a prospective randomized controlled trial to determine the safety, feasibility, and potential efficacy of RIC for patients with Parkinson's disease associated with EDS.

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“…MPTP is a Parkinsonism-inducing neurotoxin. It is a highly lipophilic molecule that can cross the blood-brain barrier (BBB) and specifically destroy dopaminergic neurons, thus MPTP is commonly used for establishment of various animal PD models ( Ke et al, 2021 ). In vitro PD models based on dopaminergic neuronal death are commonly used for identifying PD drug candidates.…”

Section: The Common Experimental Models Of Pdmentioning

confidence: 99%

The effects of bioactive components from the rhizome of gastrodia elata blume (Tianma) on the characteristics of Parkinson’s disease

Lu¹,

Qu²,

Zhong³

et al. 2022

Front. Pharmacol.

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Parkinson’s disease (PD) is an age-related chronic neurodegenerative disease caused by the death and degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The decrease of the neurotransmitter dopamine in the patient’s brain leads to various motor symptoms. PD drugs mainly enhance dopamine levels but cannot prevent or slow down the loss of dopaminergic neurons. In addition, they exhibit significant side effects and addiction issues during long-term use. Therefore, it is particularly urgent to develop novel drugs that have fewer side effects, can improve PD symptoms, and prevent the death of dopaminergic neurons. The rhizome of Gastrodia elata Blume (Tianma) is a well-known medicinal herb and has long been used as a treatment of nervous system-related diseases in China. Several clinical studies showed that formula comprising Tianma could be used as an add-on therapy for PD patients. Pharmacological studies indicated that Tianma and its bioactive components can reduce the death of dopaminergic neurons, α-synuclein accumulation, and neuroinflammation in various PD models. In this review, we briefly summarize studies regarding the effects of Tianma and its bioactive components’ effects on major PD features and explore the potential use of Tianma components for the treatment of PD.

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Comprehensive Perspectives on Experimental Models for Parkinson’s Disease

Cited by 22 publications

References 248 publications

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study

Effects of remote ischemic conditioning on sleep complaints in Parkinson's disease–rationale, design, and protocol for a randomized controlled study

The effects of bioactive components from the rhizome of gastrodia elata blume (Tianma) on the characteristics of Parkinson’s disease

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