Vagotomy and subsequent risk of <scp>P</scp>arkinson's disease

Svensson, Elisabeth; Horváth‐Puhó, Erzsébet; Thomsen, Reimar Wernich; Djurhuus, Jens Christian; Pedersen, Lars; Borghammer, Per; Sørensen, Henrik Toft

doi:10.1002/ana.24448

Cited by 641 publications

(434 citation statements)

References 30 publications

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“…Lewy pathology spreads along neural pathways and involves vagal nerves (12,15,53), and the recent observation that bilateral vagotomy reduces the risk of PD supports the concept that the causative agent in PD is transmitted from gut to the brain (19). Realizing that the disease origin has been elusive, we postulated that if EECs contained α-synuclein, they could be involved in the pathogenesis of PD.…”

Section: Discussionmentioning

confidence: 68%

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α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Chandra

Hiniker²,

Kuo³

et al. 2017

JCI Insight

175

160

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Section: Discussionmentioning

confidence: 68%

“…α-Synuclein immunoreactive inclusions have been found in neurons of the submucosal plexus, whose axons project to the mucosa (15,17,18). Moreover, it has been reported recently that bilateral vagotomy reduces the risk of PD (19).…”

Section: Introductionmentioning

confidence: 99%

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Chandra

Hiniker²,

Kuo³

et al. 2017

JCI Insight

175

160

View full text Add to dashboard Cite

“…This could explain why PD patients often suffer from olfactory and autonomic dysfunction early in disease, or even before PD diagnosis. It has been shown that total vagotomy results in a decreased PD risk, supporting the theory that the vagal nerve is involved in the pathogenesis of PD (15). In rat it has also been shown that α-synuclein can propagate from gut to brain (16) and this supports the theory that the Lewy body pathology spreads between neurons.…”

Section: List Of Papersmentioning

confidence: 58%

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

Nord¹

2017

Linköping University Medical Dissertations

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Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery.Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindrin...

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“…As mentioned above, this connection was revealed by the elimination of the CNS effects of L. rhamnosus after vagotomy 396 and by a decreased risk of certain neurologic disorders in humans who underwent vagotomy. 398 The gut microbiota also regulates key neurotransmitters, such as serotonin, by altering the precursor levels; for example, B. infantis has been shown to elevate plasma tryptophan levels and thus influence central serotonin transmission. 399 Intriguingly, the synthesis and release of neurotransmitters from bacteria has been reported.…”

Section: The Gut-brain Axismentioning

confidence: 99%

Exploring the microbiome in health and disease

Scotti

Boué

Sasso

et al. 2017

Toxicology Research and Application

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The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.

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Vagotomy and subsequent risk of Parkinson's disease

Abstract: Full truncal vagotomy is associated with a decreased risk for subsequent PD, suggesting that the vagal nerve may be critically involved in the pathogenesis of PD.

Cited by 641 publications

References 30 publications

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Levodopa pharmacokinetics -from stomach to brain : A study on patients with Parkinson’s disease

Exploring the microbiome in health and disease

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