Enteric glia are peripheral glia associated with the enteric nervous system (ENS) that function to orchestrate a variety of integrated ENS functions related to the autonomic control of gastrointestinal homeostasis. Enteric glia are also a key component of a complex gut-brain neuroepithelial circuit by which the brain quickly perceives gut sensory cues. Transcriptomics data show that enteric glia express low levels of mRNA encoding cholecystokinin (CCK) receptors A and B in the colon (35.16% and 19.36%, respectively vs P2RY1 mRNA expression, a known glia-expressed gene) and suggest that enteric glia contribute to gut-brain signalling by sensing CCK. Here, we tested the hypothesis that enteric glia detect CCK and that glial responsiveness to CCK differs among gut regions. We assessed the effects of CCK on enteric glia by using in situ Ca2+ imaging in whole-mount preparations of myenteric plexus from Sox10CreERT2::Polr2atm1[CAG-GCaMP5g,-tdTomato]Tvrd mice that express the optogenetic probe GCaMP5g in enteric glial cells. A comparable percentage of glia responded to 100µM ADP in duodenum and colon (82.4% and 89.2%, respectively; n=120 glial cells in the duodenum and n=130 in the colon), but the percentage of glia responding to 100nM CCK was higher in the colon than in the duodenum (66.4% vs 38.3%, respectively). Interestingly, blocking neuronal activity with 300nM tetrodotoxin increased the percentage of glia responding to CCK in the duodenum, but not in the colon (57.1% in the colon vs 64.8% in the duodenum). Despite higher numbers of glia responding to CCK in the colon than duodenum, CCK resulted a greater peak Ca2+ response in the duodenum than in the colon when it is compared to ADP response peak (24.8% of ADP-induced response in the colon; 33.8% of ADP-induced response in the duodenum). Glial responses to CCK in the duodenum were potentiated by blocking neuronal activity with tetrodotoxin (30% of ADP-induced response in the colon; 93.3% of ADP-induced response in the duodenum). Together, these data show that enteric glia respond to CCK and that glial responses to CCK differ in duodenum and colon. Glial sensitivity to CCK involves signalling with neurons, suggesting a possible region-specific mechanism to locally modulate gut-brain.
Regional heterogeneity of cholecystokinin sensing by enteric glia / Seguella, L; Esposito, G; Gulbransen, Bd. - (2019). (Intervento presentato al convegno XIV European Meeting on Glial cells in Health and Disease, Porto, July 10-13 2019, Portugal. tenutosi a Porto, Portugal).
Regional heterogeneity of cholecystokinin sensing by enteric glia.
Seguella L;Esposito G;
2019
Abstract
Enteric glia are peripheral glia associated with the enteric nervous system (ENS) that function to orchestrate a variety of integrated ENS functions related to the autonomic control of gastrointestinal homeostasis. Enteric glia are also a key component of a complex gut-brain neuroepithelial circuit by which the brain quickly perceives gut sensory cues. Transcriptomics data show that enteric glia express low levels of mRNA encoding cholecystokinin (CCK) receptors A and B in the colon (35.16% and 19.36%, respectively vs P2RY1 mRNA expression, a known glia-expressed gene) and suggest that enteric glia contribute to gut-brain signalling by sensing CCK. Here, we tested the hypothesis that enteric glia detect CCK and that glial responsiveness to CCK differs among gut regions. We assessed the effects of CCK on enteric glia by using in situ Ca2+ imaging in whole-mount preparations of myenteric plexus from Sox10CreERT2::Polr2atm1[CAG-GCaMP5g,-tdTomato]Tvrd mice that express the optogenetic probe GCaMP5g in enteric glial cells. A comparable percentage of glia responded to 100µM ADP in duodenum and colon (82.4% and 89.2%, respectively; n=120 glial cells in the duodenum and n=130 in the colon), but the percentage of glia responding to 100nM CCK was higher in the colon than in the duodenum (66.4% vs 38.3%, respectively). Interestingly, blocking neuronal activity with 300nM tetrodotoxin increased the percentage of glia responding to CCK in the duodenum, but not in the colon (57.1% in the colon vs 64.8% in the duodenum). Despite higher numbers of glia responding to CCK in the colon than duodenum, CCK resulted a greater peak Ca2+ response in the duodenum than in the colon when it is compared to ADP response peak (24.8% of ADP-induced response in the colon; 33.8% of ADP-induced response in the duodenum). Glial responses to CCK in the duodenum were potentiated by blocking neuronal activity with tetrodotoxin (30% of ADP-induced response in the colon; 93.3% of ADP-induced response in the duodenum). Together, these data show that enteric glia respond to CCK and that glial responses to CCK differ in duodenum and colon. Glial sensitivity to CCK involves signalling with neurons, suggesting a possible region-specific mechanism to locally modulate gut-brain.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
