scholarly journals Pramipexole and tolcapone alleviate thermal and mechanical nociception in naive rats.

Folia Medica ◽  
2021 ◽  
Vol 63 (3) ◽  
pp. 377-384
Author(s):  
Anita Mihaylova ◽  
Ilia Kostadinov ◽  
Nina Doncheva ◽  
Delian Delev ◽  
Hristina Zlatanova
Keyword(s):  
Neurodegenerative Disorder ◽  
Antinociceptive Effect ◽  
Positive Control ◽  
Motor Symptoms ◽  
Dopaminergic Drugs ◽  
Thermal Nociception ◽  
Dopaminergic Neurotransmission ◽  
Latent Time ◽  
Male Wistar Rats ◽  
Non Motor Symptoms

Introduction: Parkinson&rsquo;s disease (PD) is &#1072; neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control. Aim: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats. Materials and methods: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19. Results: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05). Conclusions: Pramipexole and tolcapone reduce mechanical and thermal nociception in na&iuml;ve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect.

scholarly journals Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Before And After ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

scholarly journals Swallowing dysfunctions in Parkinson’s disease patients: a novel challenge for the internist

2019 ◽  
Vol 13 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Elena Barbagelata ◽  
Antonello Nicolini ◽  
Paola Tognetti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Practice ◽  
Aspiration Pneumonia ◽  
Neurodegenerative Disorder ◽  
Movement Pattern ◽  
Morbidity And Mortality ◽  
Motor Symptoms ◽  
Common Causes ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a typical movement pattern, as well as different, less studied non-motor symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonia. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. The aim of this review is to identify and evaluate the existing literature on swallowing disorders in PD and providing recommendations for clinical practice routine.

scholarly journals A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

2017 ◽  
Author(s):  
Yashar Zeighami ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Ronald B. Postuma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Least Squares ◽  
Partial Least Squares ◽  
Large Scale ◽  
De Novo ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Motor Symptoms ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

scholarly journals Genotype-Phenotype Correlations in Monogenic Parkinson Disease: A Review on Clinical and Molecular Findings

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniele Guadagnolo ◽  
Maria Piane ◽  
Maria Rosaria Torrisi ◽  
Antonio Pizzuti ◽  
Simona Petrucci
Keyword(s):  
Parkinson Disease ◽  
Movement Disorders ◽  
Sleep Disturbances ◽  
Cell Function ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Mendelian Inheritance ◽  
Motor Symptoms ◽  
The Many ◽  
Non Motor Symptoms

Parkinson disease (PD) is a complex neurodegenerative disorder, usually with multifactorial etiology. It is characterized by prominent movement disorders and non-motor symptoms. Movement disorders commonly include bradykinesia, rigidity, and resting tremor. Non-motor symptoms can include behavior disorders, sleep disturbances, hyposmia, cognitive impairment, and depression. A fraction of PD cases instead is due to Parkinsonian conditions with Mendelian inheritance. The study of the genetic causes of these phenotypes has shed light onto common pathogenetic mechanisms underlying Parkinsonian conditions. Monogenic Parkinsonisms can present autosomal dominant, autosomal recessive, or even X-linked inheritance patterns. Clinical presentations vary from forms indistinguishable from idiopathic PD to severe childhood-onset conditions with other neurological signs. We provided a comprehensive description of each condition, discussing current knowledge on genotype-phenotype correlations. Despite the broad clinical spectrum and the many genes involved, the phenotype appears to be related to the disrupted cell function and inheritance pattern, and several assumptions about genotype-phenotype correlations can be made. The interest in these assumptions is not merely speculative, in the light of novel promising targeted therapies currently under development.

scholarly journals The pro-depressive effect of levodopa in a 6-OHDA-induced hemiparkinsonism rat model

2020 ◽  
Vol 48 (1) ◽  
pp. 22-33 ◽  
Author(s):  
O. S. Karimova ◽  
A. Yu. Morozova ◽  
Ya. A. Zorkina ◽  
E. A. Zubkov ◽  
V. M. Ushakova ◽  
...  
Keyword(s):  
Side Effects ◽  
Rat Model ◽  
Escape Response ◽  
Wistar Rats ◽  
Disease Model ◽  
Motor Symptoms ◽  
Depressant Effect ◽  
Male Wistar Rats ◽  
Motor Abnormalities ◽  
Non Motor Symptoms

Rationale: Treatment of Parkinson's disease has been by now symptomatic. The literature on the efficacy and side effects of levodopa has been contradictory. Some authors mention an anti-depressant effect of the agent, while others believe that it is exactly levodopa that eventually induces the occurrence of depressive symptoms. Aim: To reproduce the OHDA-hemiparkinsonism rat model with subsequent assessment of both external and structural manifestations of the disorder, as well as to study the efficacy of levodopa for motor and non-motor symptoms of parkinsonism. Materials and methods: The study was performed in 52 male Wistar rats. The disease model included stereotaxic administration of neurotoxic 6-OHDA into the pars compacta of the substantia nigra. At 2 months after the administration, the animals underwent test for motor (Rotarod, cylinder, ketamine-induced rotation in the rotometer) and non-motor abnormalities (open field, social interest, conditioned escape response). Results: In 18% of the animals no hemiparkinsonism symptoms were found. 32% of rats had only motor symptoms, whereas in 50% of the animals both motor and non-motor symptoms were noted. Levodopa could partially correct the motor abnormalities, with augmentation of depressive-like behavior. Conclusion: Levodopa has shown its partial efficacy in correction of the motor symptoms caused by administration of 6-OHDA neurotoxin; however, it caused such side effects as augmentation of depressive-like behavior and anxiety.

scholarly journals Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson’s Disease?

2021 ◽  
Vol 22 (6) ◽  
pp. 3038
Author(s):  
Javier Navarro-Zaragoza ◽  
Lorena Cuenca-Bermejo ◽  
Pilar Almela ◽  
María-Luisa Laorden ◽  
María-Trinidad Herrero
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Heat Shock ◽  
Stress Proteins ◽  
Small Heat Shock Protein ◽  
Substantia Nigra Pars Compacta ◽  
Motor Symptoms ◽  
Dopaminergic Drugs ◽  
Non Motor Symptoms

Small heat shock proteins (HSPs), such as HSP27, are ubiquitously expressed molecular chaperones and are essential for cellular homeostasis. The major functions of HSP27 include chaperoning misfolded or unfolded polypeptides and protecting cells from toxic stress. Dysregulation of stress proteins is associated with many human diseases including neurodegenerative diseases, such as Parkinson’s disease (PD). PD is characterized by the presence of aggregates of α-synuclein in the central and peripheral nervous system, which induces the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and in the autonomic nervous system. Autonomic dysfunction is an important non-motor phenotype of PD, which includes cardiovascular dysregulation, among others. Nowadays, the therapies for PD focus on dopamine (DA) replacement. However, certain non-motor symptoms with a great impact on quality of life do not respond to dopaminergic drugs; therefore, the development and testing of new treatments for non-motor symptoms of PD remain a priority. Since small HSP27 was shown to prevent α-synuclein aggregation and cytotoxicity, this protein might constitute a suitable target to prevent or delay the motor and non-motor symptoms of PD. In the first part of our review, we focus on the cardiovascular dysregulation observed in PD patients. In the second part, we present data on the possible role of HSP27 in preventing the accumulation of amyloid fibrils and aggregated forms of α-synuclein. We also include our own studies, highlighting the possible protective cardiac effects induced by L-DOPA treatment through the enhancement of HSP27 levels and activity.

scholarly journals Alpha-Synuclein and Cognitive Decline in Parkinson Disease

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1239
Author(s):  
Tian-Sin Fan ◽  
Sam Chi-Hao Liu ◽  
Ruey-Meei Wu
Keyword(s):  
Nervous System ◽  
Cognitive Impairment ◽  
Parkinson Disease ◽  
Cognitive Decline ◽  
Elderly People ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Motor Symptoms ◽  
Non Motor Symptoms ◽  
Common Neurodegenerative Disorder

Parkinson disease (PD) is the second most common neurodegenerative disorder in elderly people. It is characterized by the aggregation of misfolded alpha-synuclein throughout the nervous system. Aside from cardinal motor symptoms, cognitive impairment is one of the most disabling non-motor symptoms that occurs during the progression of the disease. The accumulation and spreading of alpha-synuclein pathology from the brainstem to limbic and neocortical structures is correlated with emerging cognitive decline in PD. This review summarizes the genetic and pathophysiologic relationship between alpha-synuclein and cognitive impairment in PD, together with potential areas of biomarker advancement.

scholarly journals Non-motor Symptoms in Parkinson’s Disease

2009 ◽  
Vol 4 (1) ◽  
pp. 25 ◽  
Author(s):  
Angelo Antonini ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Motor Symptoms ◽  
Significant Morbidity ◽  
Non Motor Symptoms ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is responsible for significant morbidity and costs. Non-motor manifestations of PD can be as disabling as the classic motor symptoms. Moreover, medications used to treat PD motor symptoms may have variable effects on these non-motor domains.

scholarly journals A Stage-Based Approach to Therapy in Parkinson’s Disease

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 388 ◽  
Author(s):  
Claudia Carrarini ◽  
Mirella Russo ◽  
Fedele Dono ◽  
Martina Di Pietro ◽  
Marianna G. Rispoli ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Symptoms ◽  
Pharmacological Management ◽  
Sleep Behavior ◽  
Heavy Burden ◽  
Non Motor Symptoms

Parkinson’s disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD.

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