Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson’s Disease Mouse Model

Berlamont, Helena; Bruggeman, Arnout; Bauwens, E; Vandendriessche, Charysse; Clarebout, Elien; Xie, Junhua; Bruyckere, Sofie De; Imschoot, Griet Van; Wonterghem, Elien Van; Ducatelle, Richard; Santens, Patrick; Smet, Annemieke; Haesebrouck, Freddy; Vandenbroucke, Roosmarijn E.

doi:10.3390/ijms222111328

Cited by 3 publications

(3 citation statements)

References 90 publications

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“…Motor function was assessed using the challenging beam traversal, pole descent, and inverted grid test as previously described ( Fleming et al, 2004 ; Sampson et al, 2016 ; Berlamont et al, 2021 ). The mice were continuously habituated in the testing room to be familiarized with the surroundings.…”

Section: Methodsmentioning

confidence: 99%

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The Spreading and Effects of Human Recombinant α-Synuclein Preformed Fibrils in the Cerebrospinal Fluid of Mice

Vandendriessche,

Bruggeman,

Foroozandeh

et al. 2024

eNeuro

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Parkinson's disease (PD) patients harbour seeding competent α-syn in their cerebrospinal fluid (CSF), which is mainly produced by the choroid plexus (ChP). Nonetheless, little is known about the role of the CSF and the ChP in PD pathogenesis. To address this question, we used an intracerebroventricular (icv) injection mouse model to assess CSF α-syn spreading and its short- and long-term consequences on the brain. Hereby, we made use of seeding competent, recombinant α-syn pre-formed fibrils (PFF) that are known to induce aggregation and subsequent spreading of endogenous α-syn in stereotactic tissue injection models. Here, we show that icv injected PFF, but not monomers (Mono), are rapidly removed from the CSF by interaction with the ChP. Additionally, shortly after icv injection both Mono and PFF were detected in the olfactory bulb and striatum. This spreading was associated with increased inflammation and complement activation in these tissues as well as leakage of the blood-CSF barrier. Despite these effects, a single icv injection of PFF didn't induce a decline in motor function. In contrast, daily icv injections over the course of five days resulted in deteriorated grip strength and formation of phosphorylated α-syn inclusions in the brain two months later, whereas dopaminergic neuron levels were not affected. These results point towards an important clearance function of the CSF and the ChP which could mediate removal of PFF from the brain, whereby chronic exposure to PFF in the CSF may negatively impact blood-CSF barrier functionality and PD pathology.Significance statementAlthough it is well known that seeding competent alpha-synuclein (α-syn) is present in cerebrospinal fluid (CSF) of Parkinson's disease (PD) patients, the CSF-spreading of pre-formed fibrils (PFF) and the following short- and long-term consequences on the brain have not yet been investigated. Here, we show that repeated PFF administration in CSF of wild-type mice results in PD-like pathology two months later, underlining the pathologic relevance of the presence of seeding competent α-syn PFF in the CSF. Furthermore, we identify the choroid plexus (ChP), an often-neglected brain region, as a potentially important player in PD pathology due to its capability to interact with CSF α-syn.

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Section: Methodsmentioning

confidence: 99%

“…Motor function was assessed using the challenging beam traversal, pole descent and inverted grid test as previously described (Fleming et al, 2004;Sampson et al, 2016;Berlamont et al, 2021).…”

Section: Motor Function Testsmentioning

confidence: 99%

The Spreading and Effects of Human Recombinant α-Synuclein Preformed Fibrils in the Cerebrospinal Fluid of Mice

Vandendriessche,

Bruggeman,

Foroozandeh

et al. 2024

eNeuro

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“…However, promising results were obtained in a study which proved inhibition of the development of MALT lymphomas after immunization based on H. felis whole cell sonicate in a mouse model challenged with H. felis [ 142 ]. Completely unexpectedly, it was recently discovered that experimental infection with H. suis in a 6-OHDA Parkinson’s disease mouse model had (partial) neuroprotective effects on Parkinson’s disease pathology, mediated by gene expression changes in brain tissue related to reduction of oxidative stress [ 143 ].…”

Section: Rodent Models In Research For Gastric Non- Helicob...mentioning

confidence: 99%

Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health

Taillieu

Chiers

Amorim

et al. 2022

Vet Res

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This article focuses on the pathogenic significance of Helicobacter species naturally colonizing the stomach of dogs, cats and pigs. These gastric “non-Helicobacter (H.) pylori Helicobacter species” (NHPH) are less well-known than the human adapted H. pylori. Helicobacter suis has been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of the pars oesophagea of the porcine stomach. The stomach of dogs and cats can be colonized by several Helicobacter species but their pathogenic significance for these animals is probably low. Helicobacter suis as well as several canine and feline gastric Helicobacter species may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, for H. suis, also consumption of contaminated pork. It has been described that standard H. pylori eradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcine H. suis strains are intrinsically less susceptible to aminopenicillins than non-human primate H. suis strains and other gastric Helicobacter species. Virulence factors of H. suis and the canine and feline gastric Helicobacter species include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors in H. pylori. It can be concluded that besides H. pylori, gastric Helicobacter species associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.

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Parkinson’s Disease, It Takes Guts: The Correlation between Intestinal Microbiome and Cytokine Network with Neurodegeneration

Xiromerisiou

Marogianni

Androutsopoulou

et al. 2023

Biology

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Parkinson’s disease is a progressive neurodegenerative disorder with motor, physical and behavioral symptoms that can have a profound impact on the patient’s quality of life. Most cases are idiopathic, and the exact mechanism of the disease’s cause is unknown. The current hypothesis focuses on the gut-brain axis and states that gut microbiota dysbiosis can trigger inflammation and advances the development of Parkinson’s disease. This systematic review presents the current knowledge of gut microbiota analysis and inflammation based on selected studies on Parkinson’s patients and experimental animal models. Changes in gut microbiota correlate with Parkinson’s disease, but only a few studies have considered inflammatory modulators as important triggers of the disease. Nevertheless, it is evident that proinflammatory cytokines and chemokines are induced in the gut, the circulation, and the brain before the development of the disease’s neurological symptoms and exacerbate the disease. Increased levels of tumor necrosis factor, interleukin-1β, interleukin-6, interleukin-17A and interferon-γ can correlate with altered gut microbiota. Instead, treatment of gut dysbiosis is accompanied by reduced levels of inflammatory mediators in specific tissues, such as the colon, brain and serum and/or cerebrospinal fluid. Deciphering the role of the immune responses and the mechanisms of the PD-associated gut microbiota will assist the interpretation of the pathogenesis of Parkinson’s and will elucidate appropriate therapeutic strategies.

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Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson’s Disease Mouse Model

Cited by 3 publications

References 90 publications

The Spreading and Effects of Human Recombinant α-Synuclein Preformed Fibrils in the Cerebrospinal Fluid of Mice

The Spreading and Effects of Human Recombinant α-Synuclein Preformed Fibrils in the Cerebrospinal Fluid of Mice

Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health

Parkinson’s Disease, It Takes Guts: The Correlation between Intestinal Microbiome and Cytokine Network with Neurodegeneration

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