scholarly journals The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 732
Author(s):  
Gianfranco Natale ◽  
Larisa Ryskalin ◽  
Gabriele Morucci ◽  
Gloria Lazzeri ◽  
Alessandro Frati ◽  
...  

The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to identifying various neuronal cytotypes belonging to ENS in baseline conditions. The second part of the study provides evidence on how these very same neurons are altered during Parkinson’s disease. In fact, although being defined as a movement disorder, Parkinson’s disease features a number of degenerative alterations, which often anticipate motor symptoms. Among these, the GI tract is often involved, and for this reason, it is important to assess its normal and pathological structure. A deeper knowledge of the ENS is expected to improve the understanding of diagnosis and treatment of Parkinson’s disease.

2019 ◽  
Vol 5 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Lanxia Meng ◽  
Xin Yuan ◽  
Xuebing Cao ◽  
Zhentao Zhang

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.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1394
Author(s):  
Michael Beekes

A neuropathological hallmark of Parkinson’s disease (PD) is the cerebral deposition of abnormally aggregated α-synuclein (αSyn). PD-associated αSyn (αSynPD) aggregates are assumed to act, in a prion-like manner, as proteinaceous nuclei (“seeds”) capable of self-templated propagation. Braak and colleagues put forward the idea of a neural gut-brain axis mediating the centripetal spread of αSynPD pathology from the enteric nervous system (ENS) to the brain in PD. This has sparked great interest and initiated passionate discussions both in support of and opposing the suggested hypothesis. A precedent for the spread of protein seeds or seeding from the gastro-intestinal (GI) tract to the central nervous system (CNS) had been previously revealed for pathological prion protein in peroral prion infections. This article scrutinizes the similarities and dissimilarities between the pathophysiological spread of disease-associated protein aggregation along the neural gut–brain axis in peroral prion infections and PD. On this basis, evidence supporting the proposed neural gut–brain axis in PD is concluded to be not as robust as that established for peroral prion infections. New tools for the ultrasensitive detection of αSynPD-associated seeding activity in archived or fresh human tissue samples such as real-time quaking induced conversion (RT-QuIC) or protein misfolding cyclic amplification (PMCA) assays can possibly help to address this deficit in the future.


2021 ◽  
pp. 107385842199226
Author(s):  
Stellina Y. H. Lee ◽  
Nathanael J. Yates ◽  
Susannah J. Tye

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson’s disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.


1996 ◽  
Vol 19 (1) ◽  
pp. 69-69
Author(s):  
A. Berardelli ◽  
R. Agostino ◽  
A. Currà ◽  
M. Manfredi

AbstractLatash & Anson's explanation of bradykinesia in patients with Parkinson's disease and cocontraction in dystonic patients is intriguing. However, the proposed adaptive changes in the central nervous system do not fit well with both clinical and experimental evidence of motor impairment in these patients. In particular, we question the explanation of: (1) the role of postural reactions and spatial accuracy in bradykinesia, (2) certain abnormalities during the execution of sequential and simultaneous movements, (3) the sudden changes in mobility (ON and OFF) of Parkinsonian patients, and (4) the meaning of reflex circuitry changes in dystonia.


2021 ◽  
Author(s):  
Ryan Hamnett ◽  
Lori Bowe Dershowitz ◽  
Vandana Sampathkumar ◽  
Ziyue Wang ◽  
Vincent De Andrade ◽  
...  

The enteric nervous system (ENS) populates the gastrointestinal (GI) tract and controls GI function. In contrast to the central nervous system, macrostructure of the ENS has been largely overlooked. Here, we visually and computationally demonstrate that the ENS is organized in circumferential stripes that regionally differ in development and neuronal composition. This characterization provides a blueprint for future understanding of region-specific GI function and identifying ENS structural correlates of GI disorders.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mark A. Fleming ◽  
Lubaina Ehsan ◽  
Sean R. Moore ◽  
Daniel E. Levin

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation, and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection, or inflammation of the ENS highlight its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI diseases including short bowel syndrome with neuronal pathophysiology and current therapies. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances and ultimately change our treatment approach.


2015 ◽  
Vol 7 (3) ◽  
Author(s):  
Celmir De Oliveira Vilaça ◽  
Marco Antonio Araujo Leite ◽  
Jano Alves De Souza ◽  
Marco Orsini ◽  
João Santos Pereira ◽  
...  

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic systems in the central nervous system. In migraine it is supposed to occur hyperactivation of central dopaminergic pathways. We verified the hypothesis of improved migraine in patients who manifest PD. We evaluated 109 patients with PD over 40 years (57 men and 52 women) about the presence throughout the life of migraine, as well as the possibility of improvement in migraine after the onset of motor symptoms of PD. This group was compared to a control group of 152 people (41 men and 152 women) without PD regarding the presence of migraine and its improvement. Twenty-one patients manifested migraine in the group with PD (16 women and 5 men) in which 13 reported improvement in migraine after the onset of symptoms of PD. Among the controls, 37 interviewed had migraine history (32 women and 5 men) among which 20 showed improvement. There was no significant difference when comparing the two groups (χ21:0,05=0.337; P<0.382). We were unable to relate the improvement of migraine with the emergence of PD motor signs, despite the degeneration of dopaminergic pathways of the central nervous system.


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