scholarly journals Cholecalciferol attenuates induced Parkinson’s like-disease variation and cellular morphology of striatum and substantial Nigra

2018 ◽  
Vol 7 (2) ◽  
pp. 1258-1273
Author(s):  
A.O. Adekeye ◽  
A.K. Adefule ◽  
P Shallie ◽  
H.B. Akpan ◽  
D.A. Adekomi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Vitamin D3 ◽  
Neurodegenerative Disorder ◽  
Antioxidant Properties ◽  
Control Group ◽  
High Dose ◽  
Motor Disorder ◽  
Mice Model

Parkinson’s disease is the commonest motor neurodegenerative disorder which affects the dopaminergic neurons and causes significant loss of dopamine. 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a selective neurotoxin in the nigrostriatal pathway leading to this motor disorder. Cholecalciferol (Vitamin D3) has been described as an active neurosteriod with antioxidant properties ubiquitously present in the brain. The study hypothesized that stimulation of vitamin D receptor by cholecalciferol could reduce autophagic cell death and degeneration following a state of drug induced parkinsonism in mice. The aim of the research was to observe the cytoarchitectural, histochemical, neurobehavioural and immunohistochemical effects of cholecalciferol on striatum and substantia nigra in mice model of MPTP-induced Parkinson’s disease. Fifty adult male C57BL/6J mice weighing about 25-35g were randomly selected and assigned into 5 groups for this study. The mice were then subjected to neurobehavioural, neurochemical and neuropathological evaluations. The results obtained showed a significant reduction (*p<0.05) in the estimated markers of oxidative stress with high dose of vitamin D3 following MPTP induction. There was also statistical significant reduction (**p<0.01, ***p<0.001) in the expression of GFAP-immuno-positive cells in the substantia nigra of the experimental mice when compared with the control group. It can be inferred that the administration of Vitamin D3 was associated with significant attenuation of focal effects linked with MPTP in mice model of Parkinson’s Disease.Keywords: Aging, Neurodegeneration, Dopaminergic neuron, Vitamin D3, Environmental toxins

Neuroprotective Effects of a GLP-2 Analogue in the MPTP Parkinson’s Disease Mouse Model

2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Dual Agonist

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

scholarly journals Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 314
Author(s):  
Aida Arroyo-Ferrer ◽  
Francisco José Sánchez-Cuesta ◽  
Yeray González-Zamorano ◽  
María Dolores del Castillo ◽  
Carolina Sastre-Barrios ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Therapy ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Cognitive Rehabilitation ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Motor Symptoms ◽  
The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease

Medicina ◽  
2011 ◽  
Vol 47 (10) ◽  
pp. 79 ◽  
Author(s):  
Sergejs Isajevs ◽  
Darja Isajeva ◽  
Ulrika Beitnere ◽  
Baiba Jansone ◽  
Ivars Kalvinsh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Substantia Nigra ◽  
Rat Model ◽  
Control Group ◽  
Western Blot Assay ◽  
Neural Cell Adhesion ◽  
6 Hydroxydopamine ◽  
Cardioprotective Drug

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM). Material and Methods. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay. Results. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values. Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.

scholarly journals Substantia nigra ferric overload and neuromelanin loss in Parkinson's disease measured with 7T MRI

2021 ◽  
Author(s):  
Catarina Rua ◽  
Claire O'Callaghan ◽  
Rong Ye ◽  
Frank Hubert Hezemans ◽  
Luca Passamonti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Resolution ◽  
Substantia Nigra ◽  
Clinical Severity ◽  
7 Tesla ◽  
Control Group ◽  
Healthy Controls ◽  
Iron Loading ◽  
Weighted Sequence

Background: Vulnerability of the substantia nigra dopaminergic neurons in Parkinson's disease is associated with ferric overload, leading to neurodegeneration with cognitive and motor decline. Here, we quantify iron and neuromelanin-related markers in vivo using ultra-high field 7-Tesla MRI, and examine the clinical correlates of these imaging assessments. Methods: Twenty-five people with mild-to-moderate Parkinson's disease and twenty-six healthy controls underwent high-resolution imaging at 7-Tesla with a T2*-weighted sequence (measuring susceptibility-χ and R2*, sensitive to iron) and a magnetization transfer-weighted sequence (MT-w, sensitive to neuromelanin). From an independent control group (N=29), we created study-specific regions-of-interest for five neuromelanin- and/or iron-rich subregions within the substantia nigra. Mean R2*, susceptibility-χ and their ratio, as well as the MT-w contrast-to-noise ratio (MT-CNR) were extracted from these regions and compared between groups. We then tested the relationships between these imaging metrics and clinical severity. Results: People with Parkinson's disease showed a significant ~50% reduction in MT-CNR compared to healthy controls. They also showed a 1.2-fold increase in ferric iron loading (elevation of the ΔR2*/Δχ ratio from 0.19±0.058ms/ppm to 0.22±0.059ms/ppm) in an area of the substantia nigra identified as having both high neuromelanin and susceptibility MRI signal in healthy controls. In this region, the ferric-to-ferrous iron loading was associated with disease duration (β=0.0072, pFDR=0.048) and cognitive impairment (β=-0.0115, pFDR=0.048). Conclusions: T2*-weighted and MT-weighted high-resolution 7T imaging markers identified neurochemical consequences of Parkinson's disease, in overlapping but not-identical regions. These changes correlated with non-motor symptoms.

Stereopsis Deficits in Parkinson’s Disease and Their Clinical Implications

2020 ◽  
Author(s):  
Fang Ba ◽  
Tina T. Sang ◽  
Jaleh Fatehi ◽  
Wenjing He ◽  
Emanuel Mostofi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Severity ◽  
Rating Scale ◽  
Disease Status ◽  
Cognitive Status ◽  
Control Group ◽  
Motor Disorder ◽  
Healthy Control ◽  
Stereo Acuity

Abstract Background: Parkinson's disease (PD) is not exclusively a motor disorder. Among non-motor features, PD patients possess sensory visual dysfunctions. Stereopsis deficit can significantly impact patients' motor performance. However, it is not routinely tested, and its significance is under-investigated. Studying stereopsis using reliable 3D stimuli may help determine its implications in disease status in PD.The objective of the study is to investigate stereopsis abnormalities in PD with reliable and more physiological tools, and their correlation with indicators of PD severity. Methods: Twenty-four healthy control and 20 PD participants were first evaluated for visual acuity, visual field, contrast acuity, and stereoperception with 2D and Titmus stereotests, followed by the assessment with the 3D active shutter system. The correlation between stereopsis and disease severity, Unified Parkinson’s disease rating scale motor scores (UPDRS-III), levodopa equivalent daily dose (LEDD), course of disease and cognitive status were evaluated using univariate regression models. Results: Screening visual tests did not reveal any differences between PD and control group. With the 3D active shutter system, PD patients demonstrated significantly worse stereopsis (i.e p=0.002, 26 seconds of arc). There was a trend that UPDRS-III and LEDD negatively correlate with the stereo acuity, suggesting poorer stereoperception is related to disease severity. Preserved cognitive function correlated with more intact stereo acuity. Conclusion: With more reliable and physiological tools, PD patients exhibit poorer stereopsis. These deficits reflected PD motor and cognitive status. How stereopsis relates to gait, fall risks and navigation warrants more investigations in the future.

Parkinson's Disease

2019 ◽  
pp. 252-273 ◽  
Author(s):  
Vaibhav Walia ◽  
Ashish Gakkhar ◽  
Munish Garg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Older Patients ◽  
Neurodegenerative Disorder ◽  
Progressive Loss ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder in which a progressive loss of the dopaminergic neurons occurs. The loss of the neurons is most prominent in the substantia nigra region of the brain. The prevalence of PD is much greater among the older patients suggesting the risk of PD increases with the increase of age. The exact cause of the neurodegeneration in PD is not known. In this chapter, the authors introduce PD, demonstrate its history, pathogenesis, neurobiology, sign and symptoms, diagnosis, and pharmacotherapy.

scholarly journals Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson’s Disease

Metabolites ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 31 ◽  
Author(s):  
Anuri Shah ◽  
Pei Han ◽  
Mung-Yee Wong ◽  
Raymond Chang ◽  
Cristina Legido-Quigley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Substantia Nigra Pars Compacta ◽  
Control Group ◽  
Sprague Dawley ◽  
Curative Therapy

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. Methods: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta. Plasma, midbrain and liver samples were collected for metabolic profiling. Multivariate and univariate analyses revealed metabolites that were altered in the PD group. Results: In plasma, palmitic acid (q = 3.72 × 10−2, FC = 1.81) and stearic acid (q = 3.84 × 10−2, FC = 2.15), were found to be increased in the PD group. Palmitic acid (q = 3.5 × 10−2) and stearic acid (q = 2.7 × 10−2) correlated with test scores indicative of motor dysfunction. Monopalmitin (q = 4.8 × 10−2, FC = −11.7), monostearin (q = 3.72 × 10−2, FC = −15.1) and myo-inositol (q = 3.81 × 10−2, FC = −3.32), were reduced in the midbrain. The liver did not have altered levels of these molecules. Conclusion: Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced PD pathology.

scholarly journals Effect of Curcumin on Protein Damage Induced by Rotenone in Dopaminergic PC12 Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2761 ◽  
Author(s):  
Sandra Buratta ◽  
Elisabetta Chiaradia ◽  
Alessia Tognoloni ◽  
Angela Gambelunghe ◽  
Consuelo Meschini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Cell Function ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Protein Damage ◽  
Substantia Nigra Pars Compacta

Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson’s by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson’s models, as well as brain tissues from Parkinson’s patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson’s disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system.

scholarly journals miR-185 and SEPT5 Genes May Contribute to Parkinson’s Disease Pathophysiology

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Arman Rahimmi ◽  
Ilaria Peluso ◽  
Aref Rajabi ◽  
Kambiz Hassanzadeh
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Chromosomal Location ◽  
Gene Expression Pattern ◽  
Control Group ◽  
Significant Difference

There are still unknown mechanisms involved in the development of Parkinson’s disease (PD), which elucidating them can assist in developing efficient therapies. Recently, studies showed that genes located on the human chromosomal location 22q11.2 might be involved in the development of PD. Therefore, the present study was designed to evaluate the role of two genes located on the chromosomal location (miR-185 and SEPT5), which were the most probable candidates based on our bibliography. In vivo and in vitro models of PD were developed using male Wistar rats and SHSY-5Y cell line, respectively. The expression levels of miR-185, SEPT5, LRRK2, and PARK2 genes were measured at a mRNA level in dopaminergic areas of rats’ brains and SHSY-5Y cells using the SYBR Green Real-Time PCR Method. Additionally, the effect of inhibition on the genes or their products on cell viability and gene expression pattern in SHSY-5Y cells was investigated. The level of miR-185 gene expression was significantly decreased in the substantia nigra (SN) and striatum (ST) of the rotenone-treated group (control group) compared to the healthy normal group (P<0.05). In addition, there was a significant difference in the expression of SEPT5 gene (P<0.05) in the substantia nigra between two studied groups. The results of an in vitro study showed no significant change in the expression of the genes; however, the inhibition on miR-185 gene expression led to the increase in LRRK2 gene expression in SHSY-5Y cells. The inhibition on LRRK2 protein also decreased the cellular toxicity effect of rotenone on SHSY-5Y cells. The results suggested the protective role of miR-185 gene in preventing the development of PD.

scholarly journals Evaluation of quality of life and psychological aspects of Parkinson's disease patients who participate in a support group

2015 ◽  
Vol 9 (3) ◽  
pp. 295-300 ◽  
Author(s):  
Nathalie Ribeiro Artigas ◽  
Vera Lúcia Widniczck Striebel ◽  
Arlete Hilbig ◽  
Carlos Roberto de Mello Rieder
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Social Phobia ◽  
Support Group ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Asymmetric Distribution ◽  
Cross Sectional

Parkinson's disease (PD) is a neurodegenerative disorder that can dramatically impair patient quality of life (QoL). Objective: To analyze the QoL, motor capacity, depression, anxiety and social phobia of individuals who attended a patient support group (PSG) compared to non-participants. Methods: A cross-sectional study was performed. The sample consisted of 20 individuals with PD who attended a PSG and another 20 PD patients who did not attend a support group for PD patients, serving as the control group (nPSG). All patients answered questionnaires on motor capacity (UPDRS), QoL (Parkinson's Disease Questionnaire- PDQ-39), depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory) and social phobia (Liebowitz Social Anxiety Scale). To determine data distribution, the Shapiro-Wilk test was performed. For comparison of means, Student's t-test was applied. In cases of asymmetry, the Mann-Whitney test was employed. To assess the association between the scales, Pearson's correlation coefficient (symmetric distribution) and Spearman's coefficient (asymmetric distribution) were applied. For the association between qualitative variables, Pearson's Chi-squared test was performed. A significance level of 5% (p≤0.05) was adopted. Results: Individuals in the PSG had a significantly better QoL (p=0.002), and lower depression (p=0.026), anxiety (p<0.001) and social phobia (p=0.01) scores compared to the nPSG. Conclusion: The participation of PD patients in social activities such as support groups is associated with better QoL and fewer symptoms of depression, anxiety and social phobia.

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