Marker-based assays for studying gut transit in gnotobiotic and conventional mouse models

Koester, Sean T.; Li, Naisi; Lachance, Daniel M.; Dey, Neelendu

doi:10.1016/j.xpro.2021.100938

Cited by 9 publications

(7 citation statements)

References 4 publications

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“…A well-known non-motor prodromal symptom of PD is GI dysfunction [3,4,46], with a prevalence of 70-80% and characterised by bloating and delayed gastric emptying [58]. We examined GI motility using carmine red, a non-absorbable dye that is well-validated for whole gastrointestinal transit time in humans [48] and rodents [32,49]. We never observed delayed expulsion of carmine-red-coloured faeces in our rotenone-treated mice.…”

Section: Discussionmentioning

confidence: 96%

“…GI symptoms are relatively common in people with PD and can include constipation or a delay in gastric emptying [46,47]. In order to examine gut motility in our model, we administered a non-absorbable dye (carmine red) and then monitored faecal pellet output over a period of 8 h. This is a well-validated test that has been used in humans [48] and rodents [32,49]. No difference in latency to expel red faecal pellets was observed (Figure 6A, time x treatment F (3, 60) = 1.7, ns).…”

Section: Intrastriatal Rotenone Causes No Change In Gastrointestinal ...mentioning

confidence: 99%

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No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease

Faisal,

Rusetskaya,

Väli

et al. 2024

Cells

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Parkinson’s disease (PD) is the second-most common neurodegenerative disorder worldwide and is diagnosed based on motor impairments. Non-motor symptoms are also well-recognised in this disorder, and peripheral neuropathy is a frequent but poorly appreciated non-motor sign. Studying how central and peripheral sensory systems are affected can contribute to the development of targeted therapies and deepen our understanding of the pathophysiology of PD. Although the cause of sporadic PD is unknown, chronic exposure to the pesticide rotenone in humans increases the risk of developing the disease. Here, we aimed to investigate whether peripheral neuropathy is present in a traditional model of PD. Mice receiving intrastriatal rotenone showed greatly reduced dopamine terminals in the striatum and a reduction in tyrosine hydroxylase-positive neurons in the Substantia nigra pars compacta and developed progressive motor impairments in hindlimb stepping and rotarod but no change in spontaneous activity. Interestingly, repeated testing using gold-standard protocols showed no change in gut motility, a well-known non-motor symptom of PD. Importantly, we did not observe any change in heat, cold, or touch sensitivity, again based upon repeated testing with well-validated protocols that were statistically well powered. Therefore, this traditional model fails to replicate PD, and our data again reiterate the importance of the periphery to the disorder.

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Section: Discussionmentioning

confidence: 96%

Section: Intrastriatal Rotenone Causes No Change In Gastrointestinal ...mentioning

confidence: 99%

No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease

Faisal,

Rusetskaya,

Väli

et al. 2024

Cells

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“…To study intestinal transit, a carmine red dye assay was used as described by Koester et al 35 Briefly, 250 µL of a sterilized 6% (w/v) solution of carmine red (Sigma-Aldrich, Milan, Italy) in 0.5% methylcellulose (Sigma-Aldrich) was delivered per mouse via oral gavage. Fecal output was monitored every 30 min or more frequently if stool passed spontaneously.…”

Section: Methodsmentioning

confidence: 99%

Disruption of the microbiota-gut-brain axis is a defining characteristic of the α-Gal A (-/0) mouse model of Fabry disease

Delprete,

Rimondini Giorgini,

Lucarini

et al. 2023

Gut Microbes

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Fabry disease (FD) is an X-linked metabolic disease caused by a deficiency in α-galactosidase A (α-Gal A) activity. This causes accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3), in different cells and organs. Neuropathic pain and gastrointestinal (GI) symptoms, such as abdominal pain, nausea, diarrhea, constipation, and early satiety, are the most frequent symptoms reported by FD patients and severely affect their quality of life. It is generally accepted that Gb3 and lyso-Gb3 are involved in the symptoms; nevertheless, the origin of these symptoms is complex and multifactorial, and the exact mechanisms of pathogenesis are still poorly understood. Here, we used a murine model of FD, the male α-Gal A (-/0) mouse, to characterize functionality, behavior, and microbiota in an attempt to elucidate the microbiota-gut-brain axis at three different ages. We provided evidence of a diarrhea-like phenotype and visceral hypersensitivity in our FD model together with reduced locomotor activity and anxiety-like behavior. We also showed for the first time that symptomology was associated with early compositional and functional dysbiosis of the gut microbiota, paralleled by alterations in fecal short-chain fatty acid levels, which partly persisted with advancing age. Interestingly, most of the dysbiotic features suggested a disruption of gut homeostasis, possibly contributing to accelerated intestinal transit, visceral hypersensitivity, and impaired communication along the gut-brain axis.

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“…Primers used for mouse genotyping are listed in the Reagents and tools table (Table 1 ). Colon transit analysis was performed as reported by Koester et al ( 2021 ). Briefly, mice (males aged 2–6 months) were submitted to oral gavage (200 µl/25 g of body weight) with Carmine red 6%–0.5% methylcellulose at 9h00.…”

Section: Methodsmentioning

confidence: 99%

The olfactory receptor Olfr78 promotes differentiation of enterochromaffin cells in the mouse colon

Dinsart,

Leprovots,

Lefort

et al. 2023

EMBO Rep

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The gastrointestinal epithelium constitutes a chemosensory system for microbiota-derived metabolites such as short-chain fatty acids (SCFA). Here, we investigate the spatial distribution of Olfr78, one of the SCFA receptors, in the mouse intestine and study the transcriptome of colon enteroendocrine cells expressing Olfr78. The receptor is predominantly detected in the enterochromaffin and L subtypes in the proximal and distal colon, respectively. Using the Olfr78-GFP and VilCre/Olfr78flox transgenic mouse lines, we show that loss of epithelial Olfr78 results in impaired enterochromaffin cell differentiation, blocking cells in an undefined secretory lineage state. This is accompanied by a reduced defense response to bacteria in colon crypts and slight dysbiosis. Using organoid cultures, we further show that maintenance of enterochromaffin cells involves activation of the Olfr78 receptor via the SCFA ligand acetate. Taken together, our work provides evidence that Olfr78 contributes to colon homeostasis by promoting enterochromaffin cell differentiation.

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Marker-based assays for studying gut transit in gnotobiotic and conventional mouse models

Cited by 9 publications

References 4 publications

No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease

No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson’s Disease

Disruption of the microbiota-gut-brain axis is a defining characteristic of the α-Gal A (-/0) mouse model of Fabry disease

The olfactory receptor Olfr78 promotes differentiation of enterochromaffin cells in the mouse colon

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