scholarly journals EXPERIMENTAL ANIMAL MODELS OF PARKINSON’S DISEASE: AN OVERVIEW

2020 ◽  
pp. 12-17
Author(s):  
MOHD IMRAN ◽  
ANURADHA MISHRA ◽  
AFREEN USMANI ◽  
ASIF EQBAL
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Current Treatment ◽  
Review Article ◽  
Transgenic Models ◽  
Slowing Down ◽  
Gradual Loss ◽  
Gait Dysfunction ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the 2nd most common neurodegenerative disorder due to gradual loss of dopaminergic nerves in the substantia nigra in the midbrain which leads to motor symptoms: For instance, gait dysfunction, involuntary tremor, rigidity, and progressive postural instability. PD has no cure and available current treatment is only symptomatic. At present, the main treatment of PD relies on Levodopa that slowing down the disease development to some level but can lead to several side effects. The literature confirms the available models of Parkinsonism that is chemical-induced, that is, by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine-induced Parkinsonism furthermore transgenic models linked to monogenic alterations in SNCA, LRRK2, UCH-L1, PRKN, and PINK1 genes. In this review article, we conclude that the presently available neurotoxic models of PD that offer a platform for neuroprotective drug discovery.

scholarly journals Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

2015 ◽  
Vol 51 (1) ◽  
pp. 111-115 ◽  
Author(s):  
Débora Dalla Vecchia ◽  
Marissa Giovanna Schamne ◽  
Marcelo Machado Ferro ◽  
Ana Flávia Chaves dos Santos ◽  
Camila Lupepsa Latyki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Hypericum Perforatum ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Turning Behavior ◽  
Age Related ◽  
Lesion Side ◽  
6 Hydroxydopamine

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

scholarly journals EFFECT OF SESAMOL IN ASSOCIATION WITH FOLIC ACID ON 6-OHDA INDUCED PARKINSONIAN ANIMALS- BIOCHEMICAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL EVIDENCE

2017 ◽  
Vol 10 (4) ◽  
pp. 46 ◽  
Author(s):  
Khadira Sereen ◽  
Vijayalakshmi K ◽  
Priya Nagappan ◽  
Shinu Balima
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Folic Acid ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Biochemical Parameter ◽  
Lesion Group ◽  
Control Group ◽  
Tbars Level ◽  
6 Hydroxydopamine

Objective: Parkinson’s disease (PD) is the world’s second neurodegenerative disorder. Degeneration of dopaminergic neurons is the hallmark of the disease. Here is a novel approach to treat PD with a phenolic compound Sesamol (SA) and in combination with Folic acid (FA).Methods: The study was designed with five groups of animals and 6 rats in each group. The rats was infused with 6-hydroxydopamine (10μg/2μl in 0.1% ascorbic acid saline) once for the development of PD, Group 1(control), Group 2(Lesion), Group 3(Lesion+ SA), Group 4(Lesion + SA+ FA) and Group 5(Lesion+ L-dopa). The biochemical parameter like glucose, triglycerides, protein, folic acid, TBARS and antioxidant profile in serum were estimated. The neurotransmitters level in striatum was estimated and histopathology of striatum and mid-brain tissues was carried out.Results: The results showed that 6-hydroxydopamine induced lesion has a significant alteration in the level of glucose, triglycerides, protein and folic acid where as TBARS level was elevated and the activities of antioxidants and neurotransmitters level were reduced. This was significantly restored on SA+FA treatment. The lesion group shows an abnormal architecture of striatum and mid-brain, whereas on SA+FA treatment there was minimal abnormality.Conclusion: Thus our study demonstrates that Sesamol has neuroprotective effect against 6-hydroxy dopamine insult and showed a synergic effect when combined with Folic acid.Keywords: Parkinson’s disease, Sesamol, Folic acid, 6-Hydroxy dopamine, Neurotransmitter, Antioxidant

The beneficial effect of vanillin on 6-hydroxydopamine rat model of Parkinson’s disease

2020 ◽  
Vol 38 (5) ◽  
pp. 369-373
Author(s):  
Rasha Abuthawabeh ◽  
Amjad N. Abuirmeileh ◽  
Karem H. Alzoubi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Beneficial Effect ◽  
Wistar Rats ◽  
Neurodegenerative Disorder ◽  
Striatal Dopamine ◽  
Intracerebral Injection ◽  
Protective Properties ◽  
Male Wistar Rats ◽  
6 Hydroxydopamine

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is related to neuroinflammation. Vanillin, which possesses both antioxidant, and anti-inflammatory properties, can be a candidate for neuroprotection in PD. Objective: This study was aimed to investigate the effects of vanillin on the 6-hydroxydopamine (6-OHDA) rodent model of PD. Methods: Male Wistar rats were administrated intraperitoneal (i.p) or oral vanillin at a dose of 20 mg/kg/day for 7 days that was started at three days before or seven days after intracerebral injection of 6-OHDA. The 6-OHDA-induced lesions were assessed behaviorally using the apomorphine rotation test, neurochemically via measuring striatal dopamine concentrations, and through immunohistochemistry. Results: Both oral and IP vanillin at three days before or seven days after 6-OHDA lesioning exhbited significantly lower tight contralateral rotations upon apomorphine challenge, and higher striatal dopamine concentrations. Conclusions: Vanillin seems to offer protective properties against 6-OHDA lesion via preserving striatal dopamine levels.

scholarly journals Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson’s Disease In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hefeng Zhou ◽  
Min Shao ◽  
Xuanjun Yang ◽  
Chuwen Li ◽  
Guozhen Cui ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Coordination ◽  
Neurodegenerative Disorder ◽  
Nerve Fibers ◽  
Substantia Nigra Pars Compacta ◽  
Neuroprotective Effects ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and there is no cure for it at present. We have previously reported that the tetramethylpyrazine (TMP) derivative T-006 exhibited beneficial effects in Alzheimer’s disease (AD) models. However, its effect on PD remains unclear. In the present study, we investigated the neuroprotective effects and underlying mechanisms of T-006 against 6-hydroxydopamine- (6-OHDA-) induced lesions in in vivo and in vitro PD models. Our results demonstrated that T-006 alleviated mitochondrial membrane potential loss and restored the energy metabolism and mitochondrial biogenesis that were induced by 6-OHDA in PC12 cells. In addition, animal experiments showed that administration of T-006 significantly attenuated the 6-OHDA-induced loss of tyrosine hydroxylase- (TH-) positive neurons in the SNpc, as well as dopaminergic nerve fibers in the striatum, and also increased the concentration of dopamine and its metabolites (DOPAC, HVA) in the striatum. Functional deficits were restored following T-006 treatment in 6-OHDA-lesioned mice, as demonstrated by improved motor coordination and rotational behavior. In addition, we found that the neuroprotective effects of T-006 were mediated, at least in part, by the activation of both the PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM pathways. In summary, our findings demonstrate that T-006 could be developed as a novel neuroprotective agent for PD, and the two pathways might be promising therapeutic targets for PD.

Assessment of Gait Disorder in Parkinson's Disease

2021 ◽  
pp. 626-644
Author(s):  
Divya Govindaraju ◽  
Gururaj Nagarajan ◽  
Paramasivam Alagumariappan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Income ◽  
Neurodegenerative Disorder ◽  
Age Group ◽  
Gait Disorder ◽  
Slowing Down ◽  
Gait Abnormality ◽  
Gait Parameters ◽  
The Brain

Neurological disorders are some of the leading chronic disorders that impose a massive burden on low-income and developing countries. The disability resulting from the neurological disorder increases the severity and costs during the primary healthcare and for entire lifetime. Parkinson's disease (PD) is the second most common chronic neurodegenerative disorder which is slowly progressive with decrease in the motor and non-motor function of the nervous system due to cognitive impairment leading to gait abnormality. PD is most common in the age group of 40-65years leading to increase in gait disorders associated with slowing down of the movement, balance instability, rigidness in the muscles, and difficulty in performing everyday tasks. The assessment of gait plays a significant role in maintaining the balance disorders in Parkinson's disease. In patients with PD, the neurons present in substantia nigra region of the brain get injured, and they progressively decline during their lifetime. Therefore, the patients lose their ability to perform movement and also lose their stability. The symptoms of PD can be monitored and controlled by assessing gait parameters based on gait disorder.

scholarly journals Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1007
Author(s):  
E. Maruthi Prasad ◽  
Shih-Ya Hung
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Neurodegenerative Disorder ◽  
Mitochondrial Respiratory Chain ◽  
Current Treatment ◽  
Muscle Rigidity ◽  
Motor Symptoms ◽  
Dopamine Depletion ◽  
Pathologic Features

Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

scholarly journals CRITICAL REVIEW OF PHARMACOGENOMICS IN ANTIPARKINSONIAN DRUG THERAPY: IMPACT ON CLINICAL MANAGEMENT OF PARKINSON’S DISEASE

2016 ◽  
Vol 9 (6) ◽  
pp. 24
Author(s):  
Poornima R ◽  
Sabreen Bashir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Critical Review ◽  
Neurodegenerative Disorder ◽  
Future Research ◽  
Comt Inhibitors ◽  
Gait Dysfunction ◽  
Non Motor Symptoms ◽  
Antiparkinsonian Drugs

Parkinson’s disease is a progressive neurodegenerative disorder characterized by rest tremors, bradykinesia , rigidity , postural instability , gait dysfunction and several non motor symptoms . The marked difference in drug response and adverse effect profile among patients led to search of genetic markers and polymorphism associated with response to antiparkinsonian drugs which will enable us to predict an individuals   response to drugs in terms of both efficacy and toxicity. Hence efforts to define the role of genetic polymorphism in optimizing pharmacotherapy of Parkinson’s disease have been undertaken and some promising genetic loci for the treatment have been determined. Therefore we aim to present a critical review of  pharmacogenetic aspects of levodopa ,  dopamine agonists and COMT inhibitors and describe gene polymorphism of interest for future research. 

scholarly journals Historical Perspective: Models of Parkinson’s Disease

2020 ◽  
Vol 21 (7) ◽  
pp. 2464 ◽  
Author(s):  
Shyh Jenn Chia ◽  
Eng-King Tan ◽  
Yin-Xia Chao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Manipulation ◽  
Disease Model ◽  
Transgenic Models ◽  
C Elegans ◽  
Wide Range ◽  
Therapeutic Development ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish, Caenorhabditis (C.) elegans, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.

scholarly journals Biomarkers and the Role of α-Synuclein in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Tingting Du ◽  
Le Wang ◽  
Weijin Liu ◽  
Guanyu Zhu ◽  
Yingchuan Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Lewy Bodies ◽  
Review Article ◽  
Tissue Imaging ◽  
Peripheral Tissues

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the presence of α-synuclein (α-Syn)-rich Lewy bodies (LBs) and the preferential loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc). However, the widespread involvement of other central nervous systems (CNS) structures and peripheral tissues is now widely documented. The onset of the molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD, so early diagnosis of PD and adequate tracking of disease progression could significantly improve outcomes for patients. Because the clinical diagnosis of PD is challenging, misdiagnosis is common, which highlights the need for disease-specific and early-stage biomarkers. This review article aims to summarize useful biomarkers for the diagnosis of PD, as well as the biomarkers used to monitor disease progression. This review article describes the role of α-Syn in PD and how it could potentially be used as a biomarker for PD. Also, preclinical and clinical investigations encompassing genetics, immunology, fluid and tissue, imaging, as well as neurophysiology biomarkers are discussed. Knowledge of the novel biomarkers for preclinical detection and clinical evaluation will contribute to a deeper understanding of the disease mechanism, which should more effectively guide clinical applications.

Emerging Pharmacotherapies for Motor Symptoms in Parkinson’s Disease

2021 ◽  
Vol 34 (4) ◽  
pp. 263-273
Author(s):  
Mohammad Al Majali ◽  
Michael Sunnaa ◽  
Pratap Chand
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Review Article ◽  
Treatment Goals ◽  
Motor Symptoms ◽  
Adequate Treatment ◽  
Advanced Therapies ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is the second commonest neurodegenerative disorder in the older adult and is characterized by progressive disabling motor symptoms of bradykinesia, tremor, rigidity, postural instability and also non motor symptoms that affect quality of life. The pharmacotherapy of PD consists of oral, transdermal, and subcutaneous medications, as well as invasive advanced therapies at later stages of the disease. PD medications are often started as monotherapy but with the progression of the illness often there is a need to add more medications and frequently comprises of a challenging polypharmacotherapy. Adverse effects of pharmacotherapy often add to the problems of adequate treatment. Patients and physicians have to prioritize treatment goals on the most disabling symptoms and the safest and most effective treatments. Almost every year newer medications and modes of delivery continue to be researched and added to the therapeutic armamentarium. This review article outlines existing and emerging pharmacotherapies for motor symptoms in PD.

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