Immunolocalization of <scp>AMPA</scp> receptor subunits within the enteric nervous system of the mouse colon and the effect of their activation on spontaneous colonic contractions

Seifi, Mohsen; Swinny, Jerome D.

doi:10.1111/nmo.12768

Cited by 18 publications

(29 citation statements)

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“…GHB is a neurotransmitter found naturally at high levels in the intestine that inhibits intestinal peristalsis via GABA B receptors and has sedative effects in the CNS [70, 71]. Glutamate is an excitatory neurotransmitter in the enteric nervous system and in the brain where it also plays an important role in synaptic plasticity [72]. The posterior insula was also associated with abundance of a subunit of butyryl-CoA:acetate CoA-transferase, an enzyme used by intestinal bacteria such as Faecalibacterium in the final step of butyrate synthesis [73, 74].…”

Section: Discussionmentioning

confidence: 99%

Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

et al. 2017

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BackgroundPreclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS.MethodsBehavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions.ResultsUsing unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory- and salience-related regions, and with a history of early life trauma.ConclusionsThe results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-017-0260-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

et al. 2017

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“…Since DNQX also reduced electrically stimulated IJPs by 41% our data indicate a role for glutamate acting at AMPA receptors within local reflex pathways activated by L-amino acids. This is a significant and novel finding since many years of investigation have revealed little evidence demonstrating a physiological role for glutamate or its receptors despite their expression on several different types of enteric neurons in guinea pigs (Galligan, 1998 ; Kirchgessner, 2001 ), rats (Burns and Stephens, 1995 ), and mice (Seifi and Swinny, 2016 ). Liu et al ( 1997 ) showed that some myenteric AH and S neurons respond to glutamate via activation of AMPA and /or NMDA receptors indicating a possible role for glutamate in synaptic transmission within the myenteric plexus but studies demonstrating a functional role for glutamate are rare.…”

Section: Discussionmentioning

confidence: 99%

Calcium Sensing Receptors Mediate Local Inhibitory Reflexes Evoked by L-Phenylalanine in Guinea Pig Jejunum

Gwynne

Parry

et al. 2017

Front. Physiol.

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Amino acids applied to the mucosa evoke inhibitory reflexes in guinea-pig jejunum, but the receptors involved in sensory transduction are still unclear. One promising candidate is the extracellular calcium sensing receptor (CaSR), which is expressed by mucosal enteroendocrine cells and is preferentially activated by aromatic L-amino acids. We tested this by applying various amino acids to the mucosa and recording the resulting inhibitory junction potentials (IJPs) in nearby circular smooth muscle via intracellular recording. The CaSR is stereospecific and L-Phenylalanine evoked a significantly larger response than D-Phenylalanine when both were applied to the same site. The same pattern was seen with L- and D-Tryptophan, another aromatic amino acid. The CaSR is preferentially activated by aromatic amino acids and responses to L-Leucine and L-Lysine were significantly lower than those to L-Phenylalanine applied to the same site. Responses to L-Phenylalanine were dose-dependently suppressed by blockade of the CaSR with NPS2143, a CaSR antagonist, and mimicked by mucosal application of cinacalcet, a CaSR agonist. Responses to cinacalcet had similar pharmacology to that of responses to L-Phenylalanine, in that each requires both P2 purinoreceptors and 5-HT receptors. L-Glutamate evoked IJPs similar to those produced by L-Phenylalanine and these were depressed by blockade of P2 receptors and 5-HT3 plus 5-HT4 receptors, but NPS2143 was ineffective. The AMPA receptor antagonists DNQX (10 μM) and CNQX (10 μM) reduced IJPs evoked by L-Glutamate by 88 and 79% respectively, but neither BAY367260 (mGluR5 antagonist) nor 2APV (NMDA antagonist) affected IJPs evoked by L-Glutamate. We conclude that local inhibitory reflexes evoked by aromatic L-amino acids in guinea pig jejunum involve activation of CaSRs which triggers release of ATP and 5-HT from the mucosa. L-Glutamate also evokes inhibitory reflexes, via a pathway that does not involve CaSRs. It is likely there are multiple receptors acting as sensory transducers for different luminal amino acids.

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“…As a major excitatory neurotransmitter in CNS, Glu plays a fundamental role in the physiological condition [25]. Despite contentious topics in the literature and that exact pathways have not yet been fully elucidated, increasing evidences suggest that glutamate may also participate in the regulation of the GI motility, as well as in the brain-gut axis [25][26][27]. NL1 is localized to glutamatergic synapses and can bind to NX1 to target the formation and differentiation of glutamatergic synapses by clustering synaptic proteins such as NR1 and VGLUT1 [15,16].…”

Section: Discussionmentioning

confidence: 99%

Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia

Wang

Gao

Zhou

et al. 2020

Gastroenterology Research and Practice

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Aim. To investigate the expressions of neuroligin1 (NL1) and neurexin1 (NX1) in a mouse model of neuronal intestinal dysplasia (Tlx2-/- mice) and to explore their effects on colonic motility. Methods. Immunohistochemistry staining was employed to explore the histological appearances of NL1, NX1, the presynaptic marker of glutamatergic synapses VGLUT1, and the subunit of NMDA receptors of NR1 in the colon of mice with or without Tlx2 mutation. Western blotting and qRT-PCR were performed to detect their relative expressions in the colon. Colonic motility was measured by a glass bead technique. Then, the Tlx2-/- mice were intervened by Huperzine A. Variations on expressions of NL1, NX1, VGLUT1, and NR1 and variations on colonic motility were measured. Additionally, serum concentrations of Glu were measured by ELISA. Results. Immunohistochemistry staining reveals that NL1, NX1, VGLUT1, and NR1 were mainly concentrated in the myenteric plexus of ENS. Compared to those in WT and Tlx2+/- mice, expressions of NL1 and NX1 in colon of Tlx2-/- mice were upregulated with increased VGLUT1 and NR1 abundances and impaired colonic motility (P<0.05). After intervention, the upregulated expressions of NL1 and NX1 were decreased with a correlated reduce of VGLUT1 and NR1 and a recovery of the impaired colonic motility (P<0.05). Variations of serum concentrations of Glu measured by ELISA were in concordance with the variations of glutamatergic synapses and colonic motility (P<0.05). Conclusion. NL1 and NX1 are closely related to the colonic motility through their effects of targeting the formation of glutamatergic synapses and may be involved in the pathogenesis of NID. The variations of serum Glu seem to be a potential and less painful auxiliary measure for colonic motility and NID.

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Immunolocalization of AMPA receptor subunits within the enteric nervous system of the mouse colon and the effect of their activation on spontaneous colonic contractions

Cited by 18 publications

References 59 publications

Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

Calcium Sensing Receptors Mediate Local Inhibitory Reflexes Evoked by L-Phenylalanine in Guinea Pig Jejunum

Effect of Neuroligin1 and Neurexin1 on the Colonic Motility in a Mouse Model of Neuronal Intestinal Dysplasia

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