Role of glial cell-line derived neurotropic factor family receptor α2 in the actions of the glucagon-like peptides on the murine intestine

2007 ◽  
Vol 293 (2) ◽  
pp. G461-G468 ◽  
Author(s):  
Sean C. McDonagh ◽  
Jenny Lee ◽  
Angelo Izzo ◽  
Patricia L. Brubaker
Keyword(s):  
Nervous System ◽  
Substance P ◽  
Enteric Nervous System ◽  
Cell Line ◽  
Glial Cell ◽  
Wild Type ◽  
Intestinal Growth ◽  
Mrna Transcripts ◽  
Neurotropic Factor

The intestinal glucagon-like peptides GLP-1 and GLP-2 inhibit intestinal motility, whereas GLP-2 also stimulates growth of the intestinal mucosa. However, the mechanisms of action of these peptides in the intestine remain poorly characterized. To determine the role of the enteric nervous system in the actions of GLP-1 and GLP-2 on the intestine, the glial cell line-derived neurotropic factor family receptor α2 (GFRα2) knockout (KO) mouse was employed. The mice exhibited decreased cholinergic staining, as well as reduced mRNA transcripts for substance P-ergic excitatory motoneurons in the enteric nervous system (ENS) ( P < 0.05). Examination of parameters of intestinal growth (including small and large intestinal weight and small intestinal villus height, crypt depth, and crypt cell proliferation) demonstrated no differences between wild-type and KO mice in either basal or GLP-2-stimulated mucosal growth. Nonetheless, KO mice exhibited reduced numbers of synaptophysin-positive enteroendocrine cells ( P < 0.05), as well as a markedly impaired basal gastrointestinal (GI) transit rate ( P < 0.05). Furthermore, acute administration of GLP-1 and GLP-2 significantly inhibited transit rates in wild-type mice ( P < 0.05–0.01) but had no effect in GFRα2 KO mice. Despite these changes, expression of mRNA transcripts for the GLP receptors was not reduced in the ENS of KO animals, suggesting that GLP-1 and -2 modulate intestinal transit through enhancement of inhibitory input to cholinergic/substance P-ergic excitatory motoneurons. Together, these findings demonstrate a role for GFRα2-expressing enteric neurons in the downstream signaling of the glucagon-like peptides to inhibit GI motility, but not in intestinal growth.

scholarly journals Primary Cilia Structure Is Prolonged in Enteric Neurons of 5xFAD Alzheimer’s Disease Model Mice

2021 ◽  
Vol 22 (24) ◽  
pp. 13564
Author(s):  
Vu Thu Thuy Nguyen ◽  
Lena Brücker ◽  
Ann-Kathrin Volz ◽  
Julia C. Baumgärtner ◽  
Malena dos Santos Guilherme ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Enteric Nervous System ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Enteric Neurons ◽  
Wild Type ◽  
5Xfad Mice

Neurodegenerative diseases such as Alzheimer’s disease (AD) have long been acknowledged as mere disorders of the central nervous system (CNS). However, in recent years the gut with its autonomous nervous system and the multitude of microbial commensals has come into focus. Changes in gut properties have been described in patients and animal disease models such as altered enzyme secretion or architecture of the enteric nervous system. The underlying cellular mechanisms have so far only been poorly investigated. An important organelle for integrating potentially toxic signals such as the AD characteristic A-beta peptide is the primary cilium. This microtubule-based signaling organelle regulates numerous cellular processes. Even though the role of primary cilia in a variety of developmental and disease processes has recently been recognized, the contribution of defective ciliary signaling to neurodegenerative diseases such as AD, however, has not been investigated in detail so far. The AD mouse model 5xFAD was used to analyze possible changes in gut functionality by organ bath measurement of peristalsis movement. Subsequently, we cultured primary enteric neurons from mutant mice and wild type littermate controls and assessed for cellular pathomechanisms. Neurite mass was quantified within transwell culturing experiments. Using a combination of different markers for the primary cilium, cilia number and length were determined using fluorescence microscopy. 5xFAD mice showed altered gut anatomy, motility, and neurite mass of enteric neurons. Moreover, primary cilia could be demonstrated on the surface of enteric neurons and exhibited an elongated phenotype in 5xFAD mice. In parallel, we observed reduced β-Catenin expression, a key signaling molecule that regulates Wnt signaling, which is regulated in part via ciliary associated mechanisms. Both results could be recapitulated via in vitro treatments of enteric neurons from wild type mice with A-beta. So far, only a few reports on the probable role of primary cilia in AD can be found. Here, we reveal for the first time an architectural altered phenotype of primary cilia in the enteric nervous system of AD model mice, elicited potentially by neurotoxic A-beta. Potential changes on the sub-organelle level—also in CNS-derived neurons—require further investigations.

scholarly journals The Role of Glial Cell Line-Derived Neurotrophic Factor in the Functioning of the Nervous System (Review)

2015 ◽  
Vol 7 (4) ◽  
pp. 211-220 ◽  
Author(s):  
T.V. Shishkina ◽  
M.V. Vedunova ◽  
T.A. Mishchenko ◽  
I.V. Mukhina
Keyword(s):  
Nervous System ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
System Review

Analysis of the role of 5-HT in the enteric nervous system using anti-idiotopic antibodies to 5-HT receptors

1994 ◽  
Vol 266 (3) ◽  
pp. G403-G416 ◽  
Author(s):  
P. R. Wade ◽  
H. Tamir ◽  
A. L. Kirchgessner ◽  
M. D. Gershon
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Substance P ◽  
Guinea Pig ◽  
Enteric Nervous System ◽  
Binding Sites ◽  
Input Resistance ◽  
Gastrointestinal Function ◽  
Postsynaptic Potentials

The effects of anti-idiotypic antibodies (alpha-id) that recognize serotonin [5-hydroxytryptamine (5-HT)] receptors on myenteric neurons of the guinea pig small intestine were characterized electrophysiologically, and alpha-id binding sites were located immunocytochemically. Initial applications of the alpha-id mimicked each of three actions of 5-HT: a rapid depolarization, associated with a fall in input resistance (Rin), which was inhibited by the 5-HT3 antagonists tropisetron (> or = 1 microM) and renzapride (100 microM); a slow membrane depolarization, associated with increased Rin, that was inhibited by the 5-HT1P antagonist renzapride but was unaffected by a 5-HT4 blocking concentration of tropisetron (10 microM); and a hyperpolarization, associated with decreased Rin, that was antagonized by the 5-HT1A inhibitor NAN-190. Cross-desensitization was observed between responses to 5-HT and the alpha-id. After exposure to the alpha-id, subsequent responses to the alpha-id, 5-HT, and stimulus-evoked slow excitatory postsynaptic potentials were antagonized; however, responses to carbachol and substance P were unaffected. The alpha-id thus specifically inhibits the effects of endogenously released and exogenously applied 5-HT. The alpha-id bound to sites on myenteric and submucosal neurons and a subepithelial nerve plexus. Binding of the alpha-id was blocked by 5-HT1P-, 5-HT3-, and 5-HT4-specific antagonists. We concluded that the alpha-id binds selectively to all known subtypes of 5-HT receptor in the enteric nervous system and is thus useful for investigating the gastrointestinal function of 5-HT.

Substance P and NK1 receptor expression in the enteric nervous system is related to the development of chagasic megacolon

2008 ◽  
Vol 102 (11) ◽  
pp. 1154-1156 ◽  
Author(s):  
Alexandre B.M. da Silveira ◽  
Michelle A.R. Freitas ◽  
Enio C. de Oliveira ◽  
Salustiano G. Neto ◽  
Alejandro O. Luquetti ◽  
...  
Keyword(s):  
Nervous System ◽  
Substance P ◽  
Enteric Nervous System ◽  
Receptor Expression ◽  
Nk1 Receptor ◽  
Chagasic Megacolon
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