Baroreflex dysfunction in Parkinson's disease: Integration of central and peripheral mechanisms

2021 ◽  
Author(s):  
Jeann L. Sabino-Carvalho ◽  
Barbara Falquetto ◽  
Ana C Takakura ◽  
Lauro C. Vianna
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Muscle Sympathetic Nerve Activity ◽  
Large Body ◽  
Cardiovascular Responses ◽  
Daily Basis ◽  
Research Area ◽  
Motor Impairments ◽  
Baroreflex Function ◽  
Reflex Arc

The incidence of Parkinson's disease (PD) is increasing worldwide. Although the PD hallmark is the motor impairments, non-motor dysfunctions are now becoming more recognized. Recently, studies have suggested that baroreflex dysfunction is one of the underlying mechanisms of cardiovascular dysregulation observed in patients with PD. However, the large body of literature on baroreflex function in PD is unclear. The baroreflex system plays a major role in the autonomic, and ultimately blood pressure and heart rate, adjustments that accompany acute cardiovascular stressors on a daily basis. Therefore, impaired baroreflex function (i.e., decreased sensitivity or gain) can lead to altered neural cardiovascular responses. Since PD affects parasympathetic and sympathetic branches of the autonomic nervous system and both are orchestrated by the baroreflex system, the understanding of this crucial mechanism in PD is necessary. In the present review, we summarize the potential altered central and peripheral mechanisms affecting the feedback controlled loops that comprise the reflex arc in patients with PD. Major factors including arterial stiffness, reduced number of C1 and activation of non-C1 neurons, presence of centrally α-synuclein aggregation, cardiac sympathetic denervation, attenuated muscle sympathetic nerve activity, and lower norepinephrine release could compromise baroreflex function in PD. Results from patients with PD and from animal models of PD will provide the reader a clearer picture on baroreflex function in this clinical condition. By doing so, our intent is to stimulate future studies to evaluate several unanswered questions in this research area.

scholarly journals Altered cardiorespiratory regulation during exercise in patients with Parkinson’s disease: A challenging non-motor feature

2020 ◽  
Vol 8 ◽  
pp. 205031212092160 ◽  
Author(s):  
Jeann L Sabino-Carvalho ◽  
Lauro C Vianna
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neural Control ◽  
Current Knowledge ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
The Body ◽  
Control Mechanisms ◽  
Motor Impairments ◽  
Patients Experience

The incidence of Parkinson’s disease is increasing worldwide. The motor dysfunctions are the hallmark of the disease, but patients also experience non-motor impairments, and over 40% of the patients experience coexistent abnormalities, such as orthostatic hypotension. Exercise training has been suggested as a coping resource to alleviate Parkinson’s disease symptoms and delay disease progression. However, the body of knowledge is showing that the cardiovascular response to exercise in patients with Parkinson’s disease is altered. Adequate cardiovascular and hemodynamic adjustments to exercise are necessary to meet the metabolic demands of working skeletal muscle properly. Therefore, since Parkinson’s disease affects parasympathetic and sympathetic branches of the autonomic nervous system and the latter are crucial in ensuring these adjustments are adequately made, the understanding of these responses during exercise in this population is necessary. Several neural control mechanisms are responsible for the autonomic changes in the cardiovascular and hemodynamic systems seen during exercise. In this sense, the purpose of the present work is to review the current knowledge regarding the cardiovascular responses to dynamic and isometric/resistance exercise as well as the mechanisms by which the body maintains appropriate perfusion pressure to all organs during exercise in patients with Parkinson’s disease. Results from patients with Parkinson’s disease and animal models of Parkinson’s disease provide the reader with a well-rounded knowledge base. Through this, we will highlight what is known and not known about how the neural control of circulation is responding during exercise and the adaptations that occur when individuals exercise regularly.

scholarly journals Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies

2021 ◽  
Author(s):  
Maarten C Hardenberg ◽  
Tessa Sinnige ◽  
Sam Casford ◽  
Samuel Dada ◽  
Chetan Poudel ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Self Assembly ◽  
Lewy Body ◽  
Amyloid Fibrils ◽  
Liquid Droplet ◽  
Large Body ◽  
Lewy Bodies ◽  
Cellular Components

Abstract Misfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large body of evidence shows that α-synuclein can aggregate into amyloid fibrils, but the relationship between α-synuclein self-assembly and Lewy body formation remains unclear. Here we show, both in vitro and in a Caenorhabditis elegans model of Parkinson’s disease, that α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-body-like properties. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro. Taken together, these results suggest that the formation of Lewy bodies may be linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.

scholarly journals Subsecond dopamine fluctuations in human striatum encode superposed error signals about actual and counterfactual reward

2015 ◽  
Vol 113 (1) ◽  
pp. 200-205 ◽  
Author(s):  
Kenneth T. Kishida ◽  
Ignacio Saez ◽  
Terry Lohrenz ◽  
Mark R. Witcher ◽  
Adrian W. Laxton ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Decision Making ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Large Body ◽  
Reward Processing ◽  
Dopamine Neurons ◽  
Model Organisms ◽  
Mammalian Brain ◽  
Prediction Errors

In the mammalian brain, dopamine is a critical neuromodulator whose actions underlie learning, decision-making, and behavioral control. Degeneration of dopamine neurons causes Parkinson’s disease, whereas dysregulation of dopamine signaling is believed to contribute to psychiatric conditions such as schizophrenia, addiction, and depression. Experiments in animal models suggest the hypothesis that dopamine release in human striatum encodes reward prediction errors (RPEs) (the difference between actual and expected outcomes) during ongoing decision-making. Blood oxygen level-dependent (BOLD) imaging experiments in humans support the idea that RPEs are tracked in the striatum; however, BOLD measurements cannot be used to infer the action of any one specific neurotransmitter. We monitored dopamine levels with subsecond temporal resolution in humans (n = 17) with Parkinson’s disease while they executed a sequential decision-making task. Participants placed bets and experienced monetary gains or losses. Dopamine fluctuations in the striatum fail to encode RPEs, as anticipated by a large body of work in model organisms. Instead, subsecond dopamine fluctuations encode an integration of RPEs with counterfactual prediction errors, the latter defined by how much better or worse the experienced outcome could have been. How dopamine fluctuations combine the actual and counterfactual is unknown. One possibility is that this process is the normal behavior of reward processing dopamine neurons, which previously had not been tested by experiments in animal models. Alternatively, this superposition of error terms may result from an additional yet-to-be-identified subclass of dopamine neurons.

Acute Cardiovascular Responses to Self-selected Intensity Exercise in Parkinson's Disease

2021 ◽  
Author(s):  
Hélcio Kanegusuku ◽  
Gabriel Grizzo Cucato ◽  
Paulo Longano ◽  
Erika Okamoto ◽  
Maria Elisa Pimentel Piemonte ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Parkinson’S Disease ◽  
Heart Rate ◽  
Parkinson's Disease ◽  
Pulse Wave ◽  
Augmentation Index ◽  
Cardiovascular Responses ◽  
Cycle Ergometer ◽  
Control Session ◽  
Wave Analysis

AbstractParkinson’s disease patients frequently present cardiovascular dysfunction. Exercise with a self-selected intensity has emerged as a new strategy for exercise prescription aiming to increase exercise adherence. Thus, the current study evaluated the acute cardiovascular responses after a session of aerobic exercise at a traditional intensity and at a self-selected intensity in Parkinson’s disease patients. Twenty patients (≥ 50 years old, Hoehn & Yahr 1–3 stages) performed 3 experimental sessions in random order: Traditional session (cycle ergometer, 25 min, 50 rpm, 60–80% maximum heart rate); Self-selected intensity: (cycle ergometer, 25 min, 50 rpm with self-selected intensity); and Control session (resting for 25 min). Before and after 30 min of intervention, brachial and central blood pressure (auscultatory method and pulse wave analysis, respectively), cardiac autonomic modulation (heart rate variability), and arterial stiffness (pulse wave analysis) were evaluated. Brachial and central systolic and diastolic blood pressure, heart rate, and the augmentation index increased after the control session, whereas no changes were observed after the exercise sessions (P<0.01). Pulse wave velocity and cardiac autonomic modulation parameters did not change after the three interventions. In conclusion, a single session of traditional intensity or self-selected intensity exercises similarly blunted the increase in brachial and central blood pressure and the augmentation index compared to a non-exercise control session in Parkinson’s disease patients.

scholarly journals Blunted cardiovascular responses to exercise in Parkinson’s disease patients: role of the muscle metaboreflex

2018 ◽  
Vol 120 (4) ◽  
pp. 1516-1524 ◽  
Author(s):  
Jeann L. Sabino-Carvalho ◽  
André L. Teixeira ◽  
Milena Samora ◽  
Maurício Daher ◽  
Lauro C. Vianna
Keyword(s):  
Blood Pressure ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cold Pressor Test ◽  
Peripheral Resistance ◽  
Cold Pressor ◽  
Cardiovascular Responses ◽  
Group Differences ◽  
Muscle Metaboreflex ◽  
Pressor Test

Patients with Parkinson’s disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex. NEW & NOTEWORTHY Patients with Parkinson’s disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.

scholarly journals Neurophysiology of the brain stem in Parkinson’s disease

2019 ◽  
Vol 121 (5) ◽  
pp. 1856-1864 ◽  
Author(s):  
Cecilia Bove ◽  
R. Alberto Travagli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Neuronal Degeneration ◽  
Alternative Hypothesis ◽  
Large Body ◽  
Substantia Nigra Pars Compacta ◽  
Clinical Feature ◽  
Motor Nucleus ◽  
Gi Symptoms

Parkinson’s disease (PD) is predominantly idiopathic in origin, and a large body of evidence indicates that gastrointestinal (GI) dysfunctions are a significant comorbid clinical feature; these dysfunctions include dysphagia, nausea, delayed gastric emptying, and severe constipation, all of which occur commonly before the onset of the well-known motor symptoms of PD. Based on a distinct distribution pattern of Lewy bodies (LB) in the enteric nervous system (ENS) and in the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), and together with the early onset of GI symptoms, it was suggested that idiopathic PD begins in the ENS and spreads to the central nervous system (CNS), reaching the DMV and the substantia nigra pars compacta (SNpc). These two areas are connected by a recently discovered monosynaptic nigro-vagal pathway, which is dysfunctional in rodent models of PD. An alternative hypothesis downplays the role of LB transport through the vagus nerve and proposes that PD pathology is governed by regional or cell-restricted factors as the leading cause of nigral neuronal degeneration. The purpose of this brief review is to summarize the neuronal electrophysiological findings in the SNpc and DMV in PD.

scholarly journals The relationships between three-axis accelerometer measures of physical activity and motor symptoms in patients with Parkinson’s disease: a single-center pilot study

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hiroto Ito ◽  
Daichi Yokoi ◽  
Rei Kobayashi ◽  
Hisashi Okada ◽  
Yasukazu Kajita ◽  
...  
Keyword(s):  
Physical Activity ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Involuntary Movement ◽  
Activity Patterns ◽  
Daily Basis ◽  
Motor Symptoms ◽  
Metabolic Equivalents ◽  
Specificity And Sensitivity ◽  
Scatter Plots

Abstract Background Various wearable devices for objectively evaluating motor symptoms of patients with Parkinson’s disease (PD) have been developed. Importantly, previous studies have suggested protective effects of physical activity in PD. However, the relationships between conventional clinical ratings for PD and three-axis accelerometer measures of physical activity (e.g., daily physical activity levels [PAL] or metabolic equivalents of task [METs]) are still unclear, particularly for METs. In the current study, we sought to elucidate these relationships on a daily basis, and to clarify optimal predictors for clinical states on a 30-min basis. Methods Patients who were hospitalized for adjustment of drugs or deep brain stimulation were enrolled. Using waist-worn three-axis accelerometers, PAL and METs parameter data were obtained and compared with UPDRS-3[On] and symptom diary data. We extracted data from the patients’ best and worst days, defined by the best and worst UPDRS-3[On] scores, respectively. Thus, 22 data sets from 11 patients were extracted. We examined the correlations and produced scatter plots to represent the relationships, then investigated which METs parameters and activity patterns were the best predictors for “On” and “dyskinesia”. Results The parameter “mean METs value within the 95–92.5 percentile range on a day (95–92.5 percentile value)” exhibited the strongest correlation with conventional daily clinical ratings (Rho: − 0.799 for UPDRS-3[On], 0.803 for On hours [p < 0.001]). Scatter plots suggested that PAL tended to have higher values in patients with involuntary movement. However, METs parameters focusing on higher METs seemed to alleviate this tendency. We clarified that “time over 2.0 METs” and “time over 1.5 METs” could be predictors for “On” and “dyskinesia” on a 30-min basis, respectively (AUROC: 0.779 and 0.959, 95% CI: 0.733–0.824 and 0.918–1.000). The specificity and sensitivity of the optimal activity pattern for “On” were 0.858 and 0.621. Conclusions This study suggested feasible activity patterns and METs parameters for objective evaluation of motor symptoms on a 30-min or daily basis. Three-axis accelerometer measures focusing on higher METs may be appropriate for evaluating physical activity. Further larger-scale studies are necessary to clarify the validity, reliability, and clinical utility of these objective measures.

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