scholarly journals Physiological and pathological changes in the enteric nervous system of rotenone-exposed mice as early biomarkers for Parkinson’s disease

2020 ◽  
Author(s):  
Gabriela Schaffernicht ◽  
Qi Shang ◽  
Alicia Stievenard ◽  
Kai Bötzel ◽  
Yanina Dening ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Enteric Neurons ◽  
Oral Exposure ◽  
Motor Symptoms ◽  
Functional Changes ◽  
Non Motor Symptoms ◽  
Mitochondrial Complex I Inhibitor

AbstractParkinson’s disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. We have shown that environmental toxins can trigger the disease by acting on the ENS and on the autonomic nervous system. Oral exposure to the pesticide rotenone, a mitochondrial Complex I inhibitor, leads to decreased stool depositions in mice. Here we analyzed the effect of rotenone on the function and structure of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations makes them ideal candidates to be used as biomarkers for the detection of Parkinson’s disease in its early stages.

scholarly journals Pathophysiological Changes in the Enteric Nervous System of Rotenone-Exposed Mice as Early Radiological Markers for Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriela Schaffernicht ◽  
Qi Shang ◽  
Alicia Stievenard ◽  
Kai Bötzel ◽  
Yanina Dening ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Adrenergic Receptors ◽  
Enteric Neurons ◽  
Motor Symptoms ◽  
Functional Changes ◽  
Non Motor Symptoms ◽  
Mitochondrial Complex I Inhibitor

Parkinson's disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. Here we analyzed the effect of the pesticide rotenone, a mitochondrial Complex I inhibitor, on the function and neuronal composition of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation (EFS). Changes in the reaction to EFS seem to be related to the reduction in the cholinergic input but also related to the noradrenergic input, as suggested by the non-adrenergic non-cholinergic (NANC) reaction to the EFS in rotenone-exposed mice. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations, that start occurring before the substantia nigra is affected in this mouse model, suggests that these alterations could be also observed in patients before the onset of motor symptoms and makes them ideal potential candidates to be used as radiological markers for the detection of Parkinson's disease in its early stages.

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 Microbiota and Parkinson's disease (overview)

2020 ◽  
pp. 10-14
Author(s):  
R. R. Tyutina ◽  
A. A. Pilipovich ◽  
V. L. Golubev ◽  
Al. B. Danilov
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Substantia Nigra ◽  
Subsequent Development ◽  
Alpha Synuclein ◽  
Intestinal Wall ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Parkinson's disease (PD) is characterized by both motor (hypokinesia, resting tremor, rigidity, postural instability) and non-motor symptoms. It is known that some non-motor manifestations, such as disturbances in smell, sleep, depression, gastrointestinal dysfunction, and others, may precede motor symptoms. Replenishment of dopamine deficiency, which, as known, develops in PD due to the death of dopaminergic neurons of the substantia nigra, makes it possible to influence most motor and some non-motor symptoms of parkinsonism, however many non-motor manifestations remain resistant to this therapy. In addition, it has only a symptomatic effect, and the pathogenetic treatment of PD is currently unavailable, which is primarily due to insufficient knowledge about the etiology and mechanisms of the development of the disease. In particular, it has already been established that alpha synuclein (a pathomorphological marker of PD) begins to be deposited in the intestinal wall, in the enteric nervous system (ENS) long before it appears in neurons of the substantia nigra. Understanding the mechanism of interaction along the axis “intestine – brain”, the role of intestinal wall dysfunction in the onset and development of PD can lead to the development of new directions in the treatment of this disease. Today, the role of microbiota, in particular the intestinal microbiota, in the functioning of the human body, its various systems, including the nervous system, is widely studied in the world. The influence of its imbalance on the activation of inflammatory reactions in the ENS and the possibility of the subsequent development of PD are considered. This review provides some evidence supporting the hypothesis that PD can be initiated in the gut. In addition, the possibilities of influencing the course of BP using pre-, pro-, syn- and metabiotics are considered.

scholarly journals Parkinson’s disease and translational research

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Elisabeth Dinter ◽  
Theodora Saridaki ◽  
Leonie Diederichs ◽  
Heinz Reichmann ◽  
Björn H. Falkenburger
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Translational Research ◽  
Dopaminergic Neurons ◽  
Therapeutic Options ◽  
Motor Symptoms ◽  
New Approaches ◽  
Biological Phenomena ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity, and when these symptoms respond to dopaminergic medications. Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states with associated pathology in various regions of the nervous system. In this review we discuss current concepts of two major alterations found during the course of the disease: cytoplasmic aggregates of the protein α-synuclein and the degeneration of dopaminergic neurons. We provide an overview of new approaches in this field based on current concepts and latest literature. In many areas, translational research on PD has advanced the understanding of the disease but there is still a need for more effective therapeutic options based on the insights into the basic biological phenomena.

scholarly journals Therapeutic Applications of Botulinum Neurotoxin for Autonomic Symptoms in Parkinson’s Disease: An Updated Review

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 226
Author(s):  
Steven D. Mitchell ◽  
Christos Sidiropoulos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Botulinum Neurotoxin ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Autonomic Nervous System Dysfunction ◽  
Autonomic Symptoms ◽  
Age Related ◽  
Non Motor Symptoms

Parkinson’s disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms associated with Parkinson’s disease include sialorrhea, hyperhidrosis, gastrointestinal dysfunction, and urinary dysfunction. Botulinum neurotoxin has been shown to potentially improve these autonomic symptoms. In this review, the varied uses of botulinum neurotoxin for autonomic dysfunction in Parkinson’s disease are discussed. This review also includes discussion of some additional indications for the use of botulinum neurotoxin in Parkinson’s disease, including pain.

scholarly journals The gut-brain axis in the pathogenesis of Parkinson’s disease

2019 ◽  
Vol 5 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Lanxia Meng ◽  
Xin Yuan ◽  
Xuebing Cao ◽  
Zhentao Zhang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Substantia Nigra ◽  
Enteric Nervous System ◽  
Lewy Bodies ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Neurodegenerative Process ◽  
The Central Nervous System

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its pathological markers include Lewy bodies and Lewy neuritis, which primarily affect the substantia nigra. However, in recent years, mounting evidence suggests that PD is a multifocal neurodegenerative process that influences several neuronal structures aside from the substantia nigra, one of which is the enteric nervous system. Many clinical studies have reported that patients with PD experience gastrointestinal dysfunction for many years before the onset of motor symptoms. Emerging evidence indicates that α-synuclein deposition may start in the enteric nervous system and then propagate to the central nervous system. The gut-brain axis plays an important role in PD pathogenesis. Recent evidence suggests that these interactions may be primarily affected by the intestinal microbiota. In this review, the authors discuss recent research, and illustrate how changes in the composition of the gut microbiota may trigger inflammation, thus contributing to neurodegeneration in PD.

scholarly journals Hypothesis of Ascension in Idiopathic Parkinson’s Disease

2017 ◽  
Vol 01 (01) ◽  
pp. E28-E35
Author(s):  
L. Klingelhoefer ◽  
H. Reichmann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Olfactory Bulb ◽  
Substantia Nigra Pars Compacta ◽  
Motor Nucleus ◽  
Motor Symptoms ◽  
Idiopathic Parkinson’S Disease ◽  
Idiopathic Parkinson's Disease ◽  
Non Motor Symptoms

AbstractDifferent clinical stages are observed in idiopathic Parkinson’s disease (PD). Non-motor symptoms define in particular the prodromal period of PD whereas primary motor symptoms such as bradykinesia with rigidity, resting tremor or postural instability are mandatory for the diagnosis of PD. Important non-motor symptoms are olfactory dysfunction, constipation, depression and sleep disturbances. Corresponding to the clinical course of PD, the Braak staging system postulates that the neuropathological process of PD starts in the enteric nervous system (ENS) of the gut and in the olfactory bulb. From there, Parkinson pathology spreads by transsynaptic cell-to-cell transfer via the sympathetic and parasympathetic nervous system in a rostrocranial direction. If the central nervous system is reached, typical neuropathological changes of PD with selective degeneration of dopaminergic neurons of the Substantia nigra pars compacta, the formation of Lewy bodies, reactive gliosis and progressive central neurodegeneration appear. Evidence of clinical, pathological and animal studies supporting these hypotheses are summarised in this review article. α-synuclein as PD-specific pathology was found in the olfactory bulb, the ENS, the submandibular gland, the intermediolateral nucleus of the spinal cord and the dorsal motor nucleus of the vagus nerve. In an animal model, in which mice are treated with the pesticide rotenone chronically and intragastrically, we could almost completely reproduce the typical pathological and clinical features of PD as well as their development in a chronological and regional sequence.

scholarly journals The Parkinson’s Real-World Impact Assessment (PRISM) Study: A European Survey of the Burden of Parkinson’s Disease in Patients and their Carers

2021 ◽  
pp. 1-15
Author(s):  
Eduardo Tolosa ◽  
Georg Ebersbach ◽  
Joaquim J. Ferreira ◽  
Olivier Rascol ◽  
Angelo Antonini ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Impact Assessment ◽  
Real World ◽  
European Countries ◽  
Life Questionnaire ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background: A greater understanding of the everyday experiences of people with Parkinson’s disease (PD) and their carers may help improve clinical practice. Objective: The Parkinson’s Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers. Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI). Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8% . Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6). Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.

scholarly journals Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson’s disease in Upper Egypt: case-control study

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Hamdy N. El-Tallawy ◽  
Tahia H. Saleem ◽  
Wafaa M. Farghaly ◽  
Heba Mohamed Saad Eldien ◽  
Ashraf Khodaery ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Motor Symptoms ◽  
And Control ◽  
Non Motor Symptoms ◽  
Control Study

Abstract Background Parkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients. Results In a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8. Conclusion Genetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

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