Colonic inflammation in Parkinson's disease

Devos, David; Lebouvier, Thibaud; Lardeux, Bernard; Biraud, Mandy; Rouaud, Tiphaine; Pouclet, Hélène; Coron, Emmanuel; Varannes, Stanislas Bruley des; Naveilhan, Philippe; Nguyen, Jean–Michel; Neunlist, Michel; Derkinderen, Pascal

doi:10.1016/j.nbd.2012.09.007

Cited by 495 publications

(453 citation statements)

References 57 publications

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“…In keeping with this hypothesis, in preliminary experiments, we found that the levels of two inflammatory parameters (tumor necrosis factor and malondialdehyde), were increased in colonic tissues from 6-OHDA rats, thus suggesting that experimental nigrostriatal denervation is associated with inflammatory activity and related oxidative stress in the colonic wall (M. Fornai, unpublished data). Of interest, our preliminary observations are consistent with the findings of a previous study, which showed an increase in proinflammatory cytokine levels and markers of glial cell activation in colonic biopsies from PD patients (Devos et al, 2013). However, the possible link between DMV-vagus nerve impairment, bowel inflammation, and development of colonic dysmotility in the setting of nigrostriatal dopaminergic neurodegeneration requires further confirmation by means of specific experimental approaches, which could represent a logical continuation of the ongoing research on this topic.…”

Section: Discussionsupporting

confidence: 90%

Enteric Dysfunctions in Experimental Parkinsons Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats

Fornai

Pellegrini

Antonioli

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Parkinson's disease is frequently associated with gastrointestinal symptoms, mostly represented by constipation and defecatory dysfunctions. This study examined the impact of central dopaminergic denervation, induced by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, on distal colonic excitatory cholinergic neuromotor activity in rats. Animals were euthanized 4 and 8 weeks after 6-OHDA injection. In vivo colonic transit was evaluated by radiologic assay. Electrically induced and carbachol-induced cholinergic contractions were recorded in vitro from longitudinal and circular muscle colonic preparations, whereas acetylcholine levels were assayed in the incubation media. Choline acetyltransferase (ChAT), HuC/D (pan-neuronal marker), muscarinic M2 and M3 receptors were assessed by immunohistochemistry or western blot assay. As compared with control rats, at week 4, 6-OHDA-treated animals displayed the following changes: decreased in vivo colonic transit rate, impaired electrically evoked neurogenic cholinergic contractions, enhanced carbachol-induced contractions, decreased basal and electrically stimulated acetylcholine release from colonic tissues, decreased ChAT immunopositivity in the neuromuscular layer, unchanged density of HuC/D immunoreactive myenteric neurons, and increased expression of colonic muscarinic M2 and M3 receptors. The majority of such alterations were also detected at week 8 post 6-OHDA injection. These findings indicate that central nigrostriatal dopaminergic denervation is associated with an impaired excitatory neurotransmission characterized by a loss of myenteric neuronal ChAT positivity and decrease in acetylcholine release, resulting in a dysregulated smooth muscle motor activity, which likely contributes to the concomitant decrease in colonic transit rate.

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Section: Discussionsupporting

confidence: 90%

Enteric Dysfunctions in Experimental Parkinsons Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats

Fornai

Pellegrini

Antonioli

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…56 Also a-synuclein deposition and the associated neurodegeneration in the enteric nervous system, characterized by increased intestinal permeability, oxidative stress and local inflammation, accounts for the constipation in PD patients. [57][58][59] These pathophysiological symptoms could be observed in the initial stages of PD, years before the important motor symptoms appear, giving support to the hypothesis that PD pathogenesis might have primary connections with the gut.…”

Section: Gut Microbiome Imbalance Affects Brain Through Microbiota-gumentioning

confidence: 52%

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Nair

Ramachandran

Joghee

et al. 2018

J Neurogastroenterol Motil

113

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Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients.

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“…Genomic studies report several pro-inflammatory factors such as IL-1β, TNF-α, IL-2, IL-6 and interferon-γ (IFN-γ) that are expressed in PD patients due to such mechanism of action [65,69]. It is also reported that, pathologically altered form of α-synuclein activates microglia and hampers the clearance of α-synuclein, which ultimately results into inflammation-mediated neurodegeneration, neuronal dysfunction, and phagocytosis [71,72]. This process is influenced by pro-inflammatory cytokines produced by microglia triggering oxidative stress [6].…”

Section: Reviewmentioning

confidence: 99%

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

Choudhury¹,

Chakraborty²,

Banerjee³

et al. 2018

Neuropsychiatry

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The pathobiology of neuronal cell loss due to various endogenous or exogenous influences is clinically termed as neurodegeneration. Neurodegeneration has been reported to be the major contributor to aging and central nervous system diseases. Apart from aging and endogenous involvement, neurodegeneration also has been reported from viral infection and prion diseases. Studies have shown that, chronic degeneration of neuronal cells initiate the pathology of Alzheimer's disease-the most prevalent neurodegenerative disorder in the world. Similar neurodegenerative pathology is also evident in Parkinson's disease, multiple sclerosis, and Amyotrophic Lateral Sclerosis. Neurodegeneration negatively affects the mental and physical functioning of the patient. Intriguingly, the involvement of inflammation has been linked as the most crucial entity in the mechanistic progress of neurodegeneration. Moreover, recent data also have shown that inflammatory biomarkers can prognosticate the silent progress of neurodegeneration through low-cost diagnostic approach. Mainly, Th17 and MDSCs are the particular immune cells, which have been reported to assist adequately to get a detailed insight into the underlying pathological process in neurodegeneration. Similarly, depression and dementia are also having a crucial association with pro-inflammatory cytokines, which in chronic spectrum indicates the degenerative pathology. Together, available literatures are depicting a direct association between neuroinflammation and neurodegeneration. In the present review, we have summed up all the neuropathologies in light of inflammation and emphasized the possible diagnostic measures by using inflammatory cells and mediators as biomarkers for neurodegenerative diseases.

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Colonic inflammation in Parkinson's disease

Cited by 495 publications

References 57 publications

Enteric Dysfunctions in Experimental Parkinsons Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats

Enteric Dysfunctions in Experimental Parkinsons Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

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