Corticotropin relessing factor (CRF) injected peripherally stimulates colonic motor function and fos expression in the lumbo-spinal cord and brain in rats

2001 ◽  
Vol 120 (5) ◽  
pp. A714-A714
Author(s):  
C MAILLOT ◽  
L WANG ◽  
M MILLION ◽  
Y TACHE
2007 ◽  
Vol 292 (1) ◽  
pp. G419-G428 ◽  
Author(s):  
L. Wang ◽  
V. Martínez ◽  
H. Kimura ◽  
Y. Taché

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5–10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 ± 1.0 cells/ganglion [ P < 0.05 vs. vehicle-treated mice (2.3 ± 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 ± 4% were also pChAT positive and 21 ± 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4 antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4 receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4 receptor-mediated colonic propulsive motor response.


2018 ◽  
Vol 314 (5) ◽  
pp. G610-G622 ◽  
Author(s):  
Seiichi Yakabi ◽  
Lixin Wang ◽  
Hiroshi Karasawa ◽  
Pu-Qing Yuan ◽  
Kazuhiko Koike ◽  
...  

We investigated whether vasoactive intestinal peptide (VIP) and/or prostaglandins contribute to peripheral corticotropin-releasing factor (CRF)-induced CRF1 receptor-mediated stimulation of colonic motor function and diarrhea in rats. The VIP antagonist, [4Cl-D-Phe6, Leu17]VIP injected intraperitoneally completely prevented CRF (10 µg/kg ip)-induced fecal output and diarrhea occurring within the first hour after injection, whereas pretreatment with the prostaglandins synthesis inhibitor, indomethacin, had no effect. In submucosal plexus neurons, CRF induced significant c-Fos expression most prominently in the terminal ileum compared with duodenum and jejunum, whereas no c-Fos was observed in the proximal colon. c-Fos expression in ileal submucosa was colocalized in 93.4% of VIP-positive neurons and 31.1% of non-VIP-labeled neurons. CRF1 receptor immunoreactivity was found on the VIP neurons. In myenteric neurons, CRF induced only a few c-Fos-positive neurons in the ileum and a robust expression in the proximal colon (17.5 ± 2.4 vs. 0.4 ± 0.3 cells/ganglion in vehicle). The VIP antagonist prevented intraperitoneal CRF-induced c-Fos induction in the ileal submucosal plexus and proximal colon myenteric plexus. At 60 min after injection, CRF decreased VIP levels in the terminal ileum compared with saline (0.8 ± 0.3 vs. 2.5 ± 0.7 ng/g), whereas VIP mRNA level detected by qPCR was not changed. These data indicate that intraperitoneal CRF activates intestinal submucosal VIP neurons most prominently in the ileum and myenteric neurons in the colon. It also implicates VIP signaling as part of underlying mechanisms driving the acute colonic secretomotor response to a peripheral injection of CRF, whereas prostaglandins do not play a role. NEW & NOTEWORTHY Corticotropin-releasing factor (CRF) in the gut plays a physiological role in the stimulation of lower gut secretomotor function induced by stress. We showed that vasoactive intestinal peptide (VIP)-immunoreactive neurons in the ileal submucosal plexus expressed CRF1 receptor and were prominently activated by CRF, unlike colonic submucosal neurons. VIP antagonist abrogated CRF-induced ileal submucosal and colonic myenteric activation along with functional responses (defecation and diarrhea). These data point to VIP signaling in ileum and colon as downstream effectors of CRF.


2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.


1992 ◽  
Vol 580 (1-2) ◽  
pp. 172-179 ◽  
Author(s):  
Elizabeth Bullitt ◽  
Chong Lam Lee ◽  
Alan R. Light ◽  
Helen Willcockson

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