Innervation peptidergique de la Muscularis mucosae : etude in vitro chez le chien

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Axe cerveau-intestin et contrôle de la prise alimentaire (exemple d'altérations chez un modèle animal de schizophrénie)

L axe cerveau-intestin désigne l interaction bidirectionnelle entre le cerveau et le tube digestif. Bien que la leptine, hormone produite par le tissu adipeux, participe à la régulation de cet axe, son mode d action dans le système nerveux entérique a été peu étudié. A l heure actuelle, une relation étroite entre une perturbation de l axe cerveau-intestin et la schizophrénie est supposée. Par conséquent, les objectifs de ce travail étaient d évaluer 1) les effets ex vivo de la leptine dans la neurotransmission entérique chez le rat et 2) les altérations périphériques dans un modèle neurodéveloppemental de la schizophrénie (NVHL) chez le rat. Nous avons montré que la leptine module l activité des neurones entériques inhibiteurs et excitateurs dans le jéjunum et le côlon proximal. L implication des neurones afférents primaires intrinsèques a été discutée. Chez les rats NVHL, nous avons mis en évidence une réduction de la masse corporelle, des variations hormonales, une inflammation du jéjunum et des altérations motrices digestives. La relation entre les troubles périphériques, notamment vagaux, et la physiopathologie de la schizophrénie a été discutée.The brain-gut axis refers to the bidirectional interaction between the gut and the brain. Although leptin, a hormone released from fat tissue, is involved in the brain-gut axis control, its mechanism of action in the enteric nervous system has not been studied so far. Nowadays, brain-gut axis dysfunctions are supposed to be in close connection with schizophrenia. Therefore, the goals of this work were to determine 1) the effects of leptin on rat enteric nervous system neurotransmission and 2) peripheral alterations in the NVHL neurodevelopmental rat model of schizophrenia. We showed that leptin modulates inhibitory and excitatory enteric motor neurons activity in jejunum and proximal colon. Implication of intrinsic primary afferent neurons was discussed. In NVHL rats, we showed a decrease in body mass, some hormonal variations, jejunal inflammation and gastro-intestinal mechanical activities alterations. The relation peripheral alterations, like vagus nerve dysfunction, and the physiopathology of schizophrenia was discussed.STRASBOURG-Bib.electronique 063 (674829902) / SudocSudocFranceF

Modulation de l'activité des neurones entériques par le GABA et les polyamines

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Long term kaolinite ingestion decreased gastric emptying rate as a consequence of duodenal mucosa remodeling

Session : Basic and translational session: Gastric physiology, pathophysiologyObjective Conflicting results showed accelerated or unchanged gastric emptying after long-term supplementation of the diet with kaolinite, a clay used as a protective compound for the injured gut. We aimed to evaluate in conscious pigs, using scintigraphic imaging, the consequences of 4 weeks ingestion of 5% kaolinite on gastric emptying of a semi-solid meal. Since kaolinite ingestion could modify the absorption of nutrients, hence modulating duodeno-gastric reflex, we tested gastric emptying with and without duodenal infusion of lipids. Methods Eight pigs were surgically fitted with a duodenal catheter under general anaesthesia. After one week recovery, the animals were divided in two groups depending of the diet: the first group received 5% kaolinite whereas the second get an iso-caloric diet containing silicate microspheres used as an a-caloric control. After 4 weeks, two scintigraphic sessions were achieved one week apart; one with and one without Intralipid infusion (1ml.min-1 starting 15 minutes before the onset of the meal and continued for 2 hours) in the duodenum. Gastric emptying was measured by automated analysis of scintigraphic images obtained every two minutes during two hours post-prandial. The test meal consisted in 500 ml porridge labelled with 40 MBq 99m-Tc-Colloid. At the end of the experiment, the animals were euthanatized and the small intestine collected for histological analysis. Results Gastric emptying of porridge in the absence of intralipid was unchanged for the two groups (T1+2; 80 ± 13.7 vs 77 ± 10.3 min for kaolinite and microspheres groups, p>0.05). On the contrary, gastric emptying differed between groups in the presence of duodenal intralipid (T1/2; 514 ± 86.8 vs 302 ± 57.3 min for kaolinite and microspheres groups, p<0.01). The reduced gastric emptying rate observed after kaolinite ingestion was associated microscopically at the duodenal level only with significant decreases (p<0.05) in the number of goblet cells (0.03 ± 0.002 vs 0.05 ± 0.002/µm2 for kaolinite and microspheres) and crypts length (418 ± 26.1 vs 594 ± 43.9 µm for kaolinite and microspheres). Conclusion These results suggested that the duodenal structural changes induced by kaolinite resulted in an increased intensity of the afferent limb of the duodeno-gastric reflex

Effects of kaolinite ingestion on regulation by leptin of intrinsic nitrergic neurons activity in jejunum and proximal colon in rats

Session : Basic and translational session: Appetite regulation, satiety, obesity and nutritionInternational audienceObjective Geophagy is the deliberate ingestion of soil by humans and animals and in particular of clay minerals such as kaolinite. In humans, geophagy has been observed in many parts of the world and is especially widespread in sub-Saharan Africa. Kaolinite ingestion has been previously shown to modulate gastric emptying and intestinal transit, and to interact with the intestinal mucosa in rats (Habold et al., Voinot et al.). As the inhibitory neurotransmitter nitric oxide is largely implied in gastrointestinal functions, the first aim of this work was to evaluate the impact of an imposed ingestion of kaolinite (5%) on enteric nitrergic innervation. Furthermore, kaolinite ingestion induced hyperphagia correlated to increase of plasmatic level of leptin. As leptin was shown to affect neurotransmission in the enteric nervous system, the second aim of this study was to determine whether the responses of enteric neurons in the presence of leptin were altered after kaolinite ingestion. Methods Male Wistar rats were fed with5% kaolinite in standard food pellets during 14 and 28 days. Ex vivo organ bath technique associated with pharmacological tools was conducted to evaluate smooth muscle contractility. Results The decrease in the nerve stimulation-induced relaxation due to L-NNA, a nitric oxide synthase inhibitor, was significantly reduced in the jejunum whereas the contraction was enhanced in the proximal colon at 14 days of kaolinite ingestion. Leptin inhibitory effects on relaxation in control animals were abolished in rats at 14 days of kaolinite ingestion. In the presence of L-NNA, leptin showed no effect on the relaxation in rats at 14 days of kaolinite ingestion compared to controls. Conclusion These data give evidence that kaolinite displays a reduction in the activation of intrinsic nitrergic neurons. This effect may explain the lack of leptin action in kaolinite rats. We hypothesized that kaolinite within the intestinal lumen stimulates intrinsic primary afferent neurons that project on these intrinsic nitrergic neurons. Changes in enteric nerves activities after kaolinite ingestion may also be due to non-beneficial effects such as iron deficiency and/or aluminum toxicity which are known to affect nitrergic neurotransmission

Leptin modulates enteric neurotransmission in the rat proximal colon: an in vitro study

International audienceLeptin has been shown to modulate gastrointestinal functions including nutrient absorption, growth, inflammation and to display complex effects on gut motility. Leptin receptors have also been identified within the enteric nervous system (ENS), which plays a crucial role in digestive functions. Although leptin has recently been shown to activate neurons in the ENS, the precise mechanisms involved are so far unknown. Therefore, the aim of the present study was to determine the effects of leptin on rat proximal colon smooth muscle and enteric neurons activities. The effects of exogenous leptin on tone and on responses to transmural nerve stimulation (TNS) of isolated circular smooth muscle of proximal colon in rats were investigated using an organ bath technique. The effects of a physiological concentration (0.1 μM) of leptin were also studied on tone and TNS-induced relaxation in the presence of atropine, hexamethonium, L-NG-Nitroarginine methyl ester (L-NAME) and capsazepine. Leptin caused a slight but significant decrease in tone, TNS-induced relaxation and contraction in a dose-dependent manner in colonic preparations. Cholinergic antagonists abolished the effects of 0.1 μM leptin on TNS-induced relaxation. This concentration of leptin had no further effect on relaxation in the presence of L-NAME. In the presence of capsazepine, leptin had no further effect either on tone or relaxation compared to the drug alone. In conclusion, leptin modulates the activity of enteric inhibitory and excitatory neurons in proximal colon. These effects may be mediated through nitrergic neurons. Intrinsic primary afferent neurons may be involved

Effects of kaolinite ingestion on regulation by leptin of intrinsic nitrergic neurons activity in jejunum and proximal colon in rats

Session : Basic and translational session: Appetite regulation, satiety, obesity and nutritionInternational audienceObjective Geophagy is the deliberate ingestion of soil by humans and animals and in particular of clay minerals such as kaolinite. In humans, geophagy has been observed in many parts of the world and is especially widespread in sub-Saharan Africa. Kaolinite ingestion has been previously shown to modulate gastric emptying and intestinal transit, and to interact with the intestinal mucosa in rats (Habold et al., Voinot et al.). As the inhibitory neurotransmitter nitric oxide is largely implied in gastrointestinal functions, the first aim of this work was to evaluate the impact of an imposed ingestion of kaolinite (5%) on enteric nitrergic innervation. Furthermore, kaolinite ingestion induced hyperphagia correlated to increase of plasmatic level of leptin. As leptin was shown to affect neurotransmission in the enteric nervous system, the second aim of this study was to determine whether the responses of enteric neurons in the presence of leptin were altered after kaolinite ingestion. Methods Male Wistar rats were fed with5% kaolinite in standard food pellets during 14 and 28 days. Ex vivo organ bath technique associated with pharmacological tools was conducted to evaluate smooth muscle contractility. Results The decrease in the nerve stimulation-induced relaxation due to L-NNA, a nitric oxide synthase inhibitor, was significantly reduced in the jejunum whereas the contraction was enhanced in the proximal colon at 14 days of kaolinite ingestion. Leptin inhibitory effects on relaxation in control animals were abolished in rats at 14 days of kaolinite ingestion. In the presence of L-NNA, leptin showed no effect on the relaxation in rats at 14 days of kaolinite ingestion compared to controls. Conclusion These data give evidence that kaolinite displays a reduction in the activation of intrinsic nitrergic neurons. This effect may explain the lack of leptin action in kaolinite rats. We hypothesized that kaolinite within the intestinal lumen stimulates intrinsic primary afferent neurons that project on these intrinsic nitrergic neurons. Changes in enteric nerves activities after kaolinite ingestion may also be due to non-beneficial effects such as iron deficiency and/or aluminum toxicity which are known to affect nitrergic neurotransmission

Controlled ingestion of kaolinite (5%) modulates enteric nitrergic innervation in rats

International audienceWe have previously shown that kaolinite slowed down gastric emptying and intesti- nal transit and induced changes in enteric mechanical activities. As gastric emptying and intestinal transit have been shown to be regulated by nitric oxide (NO), the effect of an imposed ingestion of kaolinite on enteric nitrergic innervation was determined. Kaolinite has also been shown to increase plasmatic levels of leptin. Therefore, the responses of enteric neurons in the presence of leptin after kaolinite ingestion were determined, and a possible role of nitrergic neurons was evaluated in rats using organ bath technique. Our results showed that kaolinite modulates activities of enteric nerves at 14 days of ingestion. Exogenous L-NNA produced a decrease in nerve stimulation (NS)-induced relaxation in both jejunum and colon of control groups. At 14 days of kaolinite ingestion, this effect of L-NNA was significantly reduced only in the jejunum. Although L-NNA did not affect NS-induced contraction in jejunum and colon of control animals, it increased the amplitude of the NS- induced contraction in the colon of rats at 14 days of kaolinite ingestion. Leptin inhibitory effects on ENS in the jejunum were also altered at 14 days of ingestion. These differences were masked in the presence of L-NNA. Our data give evidence that changes in mechanical activities induced by kaolinite might be due to alterations in inhibitory (nitrergic and/or other) innervation at 14 days of kaolinite ingestion and to modifications of leptin effects on the responses to intramural nerve stimulation