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Enteric neural circuitry relevant to peristaltic reflex. Following mucosal stimulation, 5-HT is released from enterochromaffin cells to intrinsic primary sensory neurons (with 5-HT3 and 5-HT4 receptors) and extrinsic vagal and spinal sensory neurons (with 5-HT3 receptors). Sensory neurons release calcitonin gene-regulated peptide (CGRP), substance (SP), and acetylcholine (ACh) to interneurons. Interneurons release ACh and SP orally to excitatory motorneurons while ACh is released aborally to inhibitory motorneurons. Excitatory motorneurons release ACh and SP to smooth muscle cells while inhibitory motorneurons release nitric oxide (NO), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and adenosine triphosphate (ATP) to smooth muscle cells. 5-HT also acts as an excitatory modulator on motor neurons (with 5-HT3 and 5-HT4 receptors) whereas dopamine seems to be an inhibitory modulator on motor neurons (with D2 receptor). Interstitial cells of Cajal (ICC) interact with smooth muscle cells for generating rhythmicity (with Ach, VIP, and NO receptors).
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Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The b...
Contexts in source publication
Context 1
... has been identified in the myenteric (Auerbach's) and submucous (Meisner's) plexuses, where interstitial cells of Cajal (ICC) exist [106]. The peristaltic reflex consists of two components: ascending contraction oral to, and descending relaxation caudal to, the site of stimulus (Figure 4). The reflex can be evoked by surface stroking or by circumfer- ential stretch [100], in which 5-HT stimulates the sensory nerve terminals [107]. ...Context 2
... patients with a supra-sacral spinal cord lesion, reflexive erection might be preserved, whereas psychogenic erection is severely disturbed because of a lesion in the spinal pathways to the sacral cord. Libido and erection are thought to be regulated by the hypothalamus; particularly the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) (Figure 4) [226,227]. Electrical or chemical stimulation in the MPOA/PVN evoked erection and mating behaviors in experimental animals, both of which were abolished by destruction of these areas. ...Similar publications
Achalasia is a rare esophageal motor disorder in the pediatric population, it is characterized by symptoms that mimic common diseases in children as gastroesophageal reflux disease (GERD), behavioral and eating disorders (ED). The clinical spectrum in children can range from typical symptoms such as progressive dysphagia, chest pain and weight loss...
Corticomuscular coherence (CMC) is an index utilized to indicate coherence between brain motor cortex and associated body muscles, conventionally. As an index of functional connections between the cortex and muscles, CMC research is the focus of neurophysiology in recent years. Although CMC has been extensively studied in healthy subjects and sport...
Background
Some beneficial effects of probiotics may be due to secreted probiotic-derived factors, identified as “postbiotic” mediators. The aim of this study was to evaluate whether supernatants harvested from Lactobacillus rhamnosus GG (LGG) cultures (ATCC53103 strain) protect colonic human smooth muscle cells (HSMCs) from lipopolysaccharide (LPS...
Environmental stressor exposure is associated with a variety of age-related diseases including neurodegeneration. Although the initial events of sporadic Parkinson's disease (PD) are not known, consistent evidence supports the hypothesis that the disease results from the combined effect of genetic and environmental risk factors. Among them, behavio...
Acute bacterial meningitis has a global mortality rate of 135000 cases per year. In Argentina over the last 12 years, the annual incidence rate has been 5.5/100 000. About 20% of patients present neurological sequelae, which are more common in patients aged 60 or older. Our objective here is to determine the clinical characteristics, the most commo...
Citations
... Tersiyer SD, seksüel davranışları etkileyen psikolojik, sosyokültürel kaygılar ve düşük özgüven ile ilişkilidir. Bu değişkenler anksiyete, düşük özsaygı, evlilik ve aile rollerinde değişiklikler, vücut imajında değişiklikler, partner tarafından reddedilme korkusu gibi durumları içerir 13,14 . Bu semptomlar seksüel yanıt döngüsünün herhangi bir aşamasını ya da tamamını etkilemektedir. ...
... The lower bowel (descending colon, sigmoid colon, and rectum) share sacral innervation with the LUT, modulated by the higher brain structures including the frontal lobe, the hypothalamus, and the basal ganglia. 29 Most areas activated in functional neuroimaging by bowel distention 30 strikingly overlap the area activated by bladder distention. ...
Objectives: Several central nervous system (CNS) centers affect muscle groups of the lower urinary tract (LUT) and anorectal tract (ART) via autonomic and somatic pathways, working in different modes (storage or expulsion). Hence spinal cord dysfunction can affect the LUT and ART by several possible mechanisms.
Methods: This review reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities of spinal dysfunction.
Results: Discussion focussed on the levator ani nerve, mechanisms underpinning sensory function and sensation, functional imaging, dyssynergia, and experimental models. The following key research questions were identified. (1) Clinically, how can we evaluate the levator ani muscle to support assessment and identify prognosis for effective treatment selection? (2) How can we reliably measure levator ani tone? (3) How can we evaluate sensory information and sensation for the LUT and the ART? (4) What is the role of functional CNS imaging in development of scientific insights and clinical evaluation? (5) What is the relationship of detrusor sphincter dyssynergia to renal failure?
Conclusions: Spinal cord dysfunction can fundamentally disrupt LUT and ART function, with considerable clinical impact. The evaluation needs to reflect the full scope of potential problems, and new clinical and diagnostic approaches are needed, for prognosis and treatment. The preclinical science evaluating spinal cord function in both LUT and ART storage and elimination remains a major priority, even though it is a challenging experimental context. Without this underpinning evidence, development of new clinical evidence may be held back.
... Apomorphine Apomorphine can stimulate dopamine D2 receptors and activate oxytocin neurons in the paraventricular nucleus (PVN) [133]. When erectile dysfunction is caused by central lesions and PDE5 inhibitors fail, sublingual administration of 2 or 4 mg of apomorphine can be considered [134]. ...
... Common adverse reactions include nausea, flushing, stretching and yawning [125]. In addition, recent melanocortin tests have shown that melanotan II and bremelanotide may become an option for the treatment of erectile dysfunction when PDE5 inhibitors are ineffective [133]. ...
... Dopamine D2 receptor blockers Dopaminergic blockers such as domperidone can promote gastrointestinal motility by antagonizing the inhibitory effect of dopamine on gastrointestinal motility. Studies have indicated that domperidone can improve constipation and delay gastric emptying in patients with PD [133]. The usual dosage is 10-40 mg four times a day. ...
Multiple system atrophy (MSA) is a sporadic, fatal, and rapidly progressive neurodegenerative disease of unknown etiology that is clinically characterized by autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. Early onset and extensive autonomic dysfunction, including cardiovascular dysfunction characterized by orthostatic hypotension (OH) and supine hypertension, urinary dysfunction characterized by overactive bladder and incomplete bladder emptying, sexual dysfunction characterized by sexual desire deficiency and erectile dysfunction, and gastrointestinal dysfunction characterized by delayed gastric emptying and constipation, are the main features of MSA. Autonomic dysfunction greatly reduces quality of life and increases mortality. Therefore, early diagnosis and intervention are urgently needed to benefit MSA patients. In this review, we aim to discuss the systematic treatment of autonomic dysfunction in MSA, and focus on the current methods, starting from non-pharmacological methods, such as patient education, psychotherapy, diet change, surgery, and neuromodulation, to various drug treatments targeting autonomic nerve and its projection fibers. In addition, we also draw attention to the interactions among various treatments, and introduce novel methods proposed in recent years, such as gene therapy, stem cell therapy, and neural prosthesis implantation. Furthermore, we elaborate on the specific targets and mechanisms of action of various drugs. We would like to call for large-scale research to determine the efficacy of these methods in the future. Finally, we point out that studies on the pathogenesis of MSA and pathophysiological mechanisms of various autonomic dysfunction would also contribute to the development of new promising treatments and concepts.
... Дисфункция кишечника проявляется запорами, диареей или недержанием кала. К изменениям в сексуальной сфере относят эректильную дисфункцию, снижение либидо, аноргазмию, сухость влагалища [1][2][3][4]. ...
... 24 2 0 2 3 ANDROLOGY AND GENITAL SURGERY Оригинальная статья / Original report до 79 %, половая функция -от 50 % [9][10][11]). Это приводит к значительному снижению качества жизни пациентов и увеличению нагрузки на систему здравоохранения [1,12,13]. ...
Background . Dysfunction of the bladder and intestinal tract, as well as sexual disorders, can be caused by pathologies of the pelvic organs themselves or changes in the control of these organs by the nervous system. Modern questionnaires are organ-specific and are intended for specific neurological disorders. Questionnaire on pelvic organ function is a valuable instrument for evaluation of complaints from neurological patients, therefore there is a necessity of creating an official adapted Russian version.
Aim . Creation of a Russian-language version of the pelvic organ function questionnaire and its validation on a cohort of patients with neurological diseases.
Materials and methods . Following international standards, validation of the questionnaire included linguistic and cultural adaptation and assessment of its psychometric properties. Approval of the Russian-language questionnaire version was obtained directly from the developer, Ryuji Sakakibara. The questionnaire was tested twice – before and after treatment. There were 48 patients over 18 years old (18 with Parkinson’s disease, 15 with multiple sclerosis, and 15 post-stroke).
Results . The Median (IQR) age of patients was 56.5 (42–70.5) years. A Russian-language version of the questionnaire was developed during linguistic and cultural adaptation. This version of the questionnaire is posted in the text of this publication. It is also available on the website of the validation group of the international scales and questionnaires of the Research Center of Neurology. At the 2nd stage of validation, it was shown that the mean score in the sample was 2.03 ± 0.52 per question upon admission to the hospital and decreased significantly to 1.91 ± 0.51 per question on discharge (Wilcoxon test, p ˂ 0.0001). It confirms the questionnaire’s high sensitivity to changes in the clinical picture. Cronbach’s alpha coefficient was 0.82 (p ˂ 0.001).It indicates the high level of internal consistency of the questionnaire. Significant Spearman’s coefficients prove criterion validity of the studied questionnaire compared to the established questionnaires.
Conclusion . This Russian-language version of the pelvic organ function questionnaire is a useful assessment tool for patients’ complaints and disease dynamics. This work is valuable as an example of adapting a foreign scale or questionnaire to the local health care system.
... This pathway is relevant to not only motor but also cognitive [81], mental [82], and autonomic nervous system function [83]. There is growing evidence that a PFC-nigrostriatal D1 dopaminergic pathway inhibits the micturition reflex [84,85], possibly via the GABAergic collateral from the direct pathway of the basal ganglia motor circuit or via the PFC as a bidirectional projection from the circuit [86,87]. Since the nigrostriatal system is one of the centers controlling muscle tone and movement, LUT dysfunction originating from this area is closely related to motor disorder [88]. ...
This article reviewed brain mechanism of the lower urinary tract (LUT). Among autonomic nervous systems, LUT is unique in terms of afferent pathophysiology; bladder sensation is perceived soon after the storage phase and throughout the voiding phase. Within the brain, this is measured in experimental animals by the firing of single neurons and in humans by evoked potentials/functional neuroimaging. The evidence indicates that sphincter information goes up to the precentral motor cortex and other brain areas, and bladder information goes up to the insular cortex (IC)/anterior cingulate (ACG) and further to the prefrontal cortex (PFC). Another LUT-specific phenomenon is efferent pathophysiology: detrusor overactivity (exaggerated micturition reflex) occurs in brain diseases such as stroke (focal disease) and dementia with Lewy bodies (diffuse diseases, may overlap with each other). With the turning off and on of the brain-switch of micturition (at the periaqueductal gray [PAG]), there is a bladder-inhibitory PFC-IC/ACG-hypothalamus-PAG pathway, with interconnections via the PFC with a PFC-nigrostriatal D1 dopaminergic pathway and a PFC-cerebellar pathway. Brain diseases that affect these areas may cause a loss of the brain's inhibition of the micturition reflex, leading to detrusor overactivity. This has a significant clinical impact on patients and requires appropriate management.
... Neurophysiological observations can lead to the hypothesis that a decrease of DA from a central perspective, rather results in diuresis [148] and/or DO [108]; and perhaps drives the underlying mechanism of the co-occurrence of both RLS and nocturia. A phenomenon which can be seen e.g. in PD patients [149][150][151]. ...
Introduction:
Aging is associated with a combination of several lower urinary tract (LUT) signs and symptoms, including residual urine, overactive bladder and nocturia. One of the mechanisms of this LUT dysfunction that has not been discussed in dept so far is the role of dopamine (DA).
Methods:
In this narrative review, we explore the dopaminergic hypothesis in the development of this combination of LUT signs and symptoms in older adults.
Results:
DA is one of the neurotransmitters whose regulation and production is disrupted in aging. In synucleinopathies, altered DAergic activity is associated with the occurrence of LUTS and sleep disorders. Projections of DAergic neurons are involved in the regulation of sleep, diuresis, and bladder activity. The low dopamine hypothesis could explain the genesis of a set of LUT signs and symptoms commonly seen in this population, including elevated residual urine, Overactive bladder syndrome and Nocturia (discussed as the RON syndrome). This presentation is however also common in older patients without synucleinopathies or neurological disorders and therefore we hypothesise that altered DAergic activity because of pathological aging, and selective destruction of DAergic neurons, could underpin the presentation of this triad of LUT dysfunction in the older population.
Conclusion:
The concept of RON syndrome helps to better understand this common phenotypic presentation in clinical practice, and therefore serves as a useful platform to diagnose and treat LUTS in older adults. Besides recognizing the synucleinopathy "red flag" symptoms, this set of multi-causal LUT signs and symptoms highlights the inevitable need for combination therapy, a challenge in older people with their comorbidities and concomitant medications.
... One of the most common non-motor symptoms that significantly affect the quality of life of patients with Parkinson's disease (PD) is gastrointestinal dysfunction, which includes constipation, diarrhea, and fecal incontinence (for reviews see References [1,2]). Clinical studies have shown that more than half of all PD patients report decreased frequency of defecation and problems with stool expulsions, which is a significantly higher ratio as compared with healthy subjects [3,4]. ...
... The mechanisms behind these troublesome non-motor symptoms in PD are poorly understood. The disorder is known to affect both the enteric nervous system as well as the central nervous system [2], which may both be responsible for the development of the gastrointestinal problems. To elucidate the mechanisms, most studies have used the 6-hydroxydopamine (6-OHDA) rat model of PD [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. ...
Background:
Gastrointestinal dysfunction is one of the most common non-motor symptoms in Parkinson's disease (PD). The exact mechanisms behind these symptoms are not clearly understood. Studies in the well-established 6-hydroxydopamine (6-OHDA) lesioned rats of PD have shown altered contractility in isolated circular and longitudinal smooth muscle strips of distal colon. Contractile changes in proximal colon and distal ileum are nevertheless poorly studied. Moreover, segments may serve as better tissue preparations to understand the interplay between circular and longitudinal smooth muscle. This study aimed to compare changes in contractility between isolated full-thickness distal colon muscle strips and segments, and extend the investigation to proximal colon and distal ileum in the 6-OHDA rat model.
Methods:
Spontaneous contractions and contractions induced by electrical field stimulation (EFS) and by the non-selective muscarinic agonist methacholine were investigated in strip and/or segment preparations of smooth muscle tissue from distal and proximal colon and distal ileum in an in vitro organ bath comparing 6-OHDA-lesioned rats with Sham-operated animals. Key Results. Our data showed increased contractility evoked by EFS and methacholine in segments, but not in circular and longitudinal tissue strips of distal colon after central 6-OHDA-induced dopamine denervation. Changes in proximal colon segments were also displayed in high K+ Krebs-induced contractility and spontaneous contractions.
Conclusions:
This study further confirms changes in smooth muscle contractility in distal colon and to some extent in proximal colon, but not in distal ileum in the 6-OHDA rat model of PD. However, the changes depended on tissue preparation.
... This pathway is relevant to not only motor but also cognitive [81], mental [82], and autonomic nervous system function [83]. There is growing evidence that a PFC-nigrostriatal D1 dopaminergic pathway inhibits the micturition reflex [84,85], possibly via the GABAergic collateral from the direct pathway of the basal ganglia motor circuit or via the PFC as a bidirectional projection from the circuit [86,87]. Since the nigrostriatal system is one of the centers controlling muscle tone and movement, LUT dysfunction originating from this area is closely related to motor disorder [88]. ...
This article reviewed brain mechanism of the lower urinary tract (LUT). Among autonomic nervous systems, LUT is unique in terms of afferent pathophysiology; bladder sensation is perceived soon after the storage phase and throughout the voiding phase. Within the brain, this is measured in experimental animals by the firing of single neurons and in humans by evoked potentials/functional neuroimaging. The evidence indicates that sphincter information goes up to the precentral motor cortex and other brain areas, and bladder information goes up to the insular cortex (IC)/anterior cingulate (ACG) and further to the prefrontal cortex (PFC). Another LUT-specific phenomenon is efferent pathophysiology: detrusor overactivity (exaggerated micturition reflex) occurs in brain diseases such as stroke (focal disease) and dementia with Lewy bodies (diffuse diseases, may overlap with each other). With the turning off and on of the brain-switch of micturition (at the periaqueductal gray [PAG]), there is a bladder-inhibitory PFC-IC/ACG-hypothalamus-PAG pathway, with interconnections via the PFC with a PFC-nigrostriatal D1 dopaminergic pathway and a PFC-cerebellar pathway. Brain diseases that affect these areas may cause a loss of the brain's inhibition of the micturition reflex, leading to detrusor overactivity. This has a significant clinical impact on patients and requires appropriate management.
... Hypersexuality or aberrant sexual behaviors are more related to dopaminergic therapy, such as dopamine agonists (Choi et al., 2020, Rana et al., 2015. Furthermore, it is possible that dopaminergic drugs such as Levodopa and other antiparkinsonian drugs may affect sexual function in PD, although the contribution of Levedopa to improving sexual dysfunction is not yet clear (Sakakibara et al., 2011). ...
Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.
... PD has a clinical presentation of progressively worsening bradykinesia, typically accompanied by either gait disturbance, resting tremor or rigidity [125,127,128], however it is commonly accepted that PD-related neurodegeneration can begin several decades before motor symptom onset [129,130]. A range of non-motor symptoms, some of which arise prodromal to clinical onset of disease [129,130], are strong correlates of PD including autonomic dysfunction [131][132][133][134], neuropsychiatric symptoms [135][136][137][138], dementia [139,140], sensory symptoms [141,142] including loss of olfaction (which commonly predates motor symptoms ) [143] and sleep and circadian rhythm dysfunction [144][145][146]. In the following section we will summarize the sleep and circadian phenotypes in PDfor a more in-depth analysis of this see these recent reviews [3,144,[147][148][149]. ...
The use of animals as models of human physiology is, and has been for many years, an indispensable tool for understanding the mechanisms of human disease. In Parkinson’s disease, various mouse models form the cornerstone of these investigations. Early models were developed to reflect the traditional histological features and motor symptoms of Parkinson’s disease. However, it is important that models accurately encompass important facets of the disease to allow for comprehensive mechanistic understanding and translational significance. Circadian rhythm and sleep issues are tightly correlated to Parkinson’s disease, and often arise prior to the presentation of typical motor deficits. It is essential that models used to understand Parkinson’s disease reflect these dysfunctions in circadian rhythms and sleep, both to facilitate investigations into mechanistic interplay between sleep and disease, and to assist in the development of circadian rhythm-facing therapeutic treatments. This review describes the extent to which various genetically- and neurotoxically-induced murine models of Parkinson’s reflect the sleep and circadian abnormalities of Parkinson’s disease observed in the clinic.
