Central neuronal mechanisms of intestinal electrical stimulation: Effects on duodenum distention-responsive (DD-R) neurons in the VMH of rats

Abstract

Intestinal electrical stimulation (IES) has been shown to produce inhibitory effects on gastric contractions, gastric emptying, food intake and body weight in rats and dogs, suggesting a therapeutic potential for obesity. The aims of this study were 1) to test the hypothesis that the neurons in the VMH are involved in the central mechanisms of IES treatment for obesity; 2) to compare the effects of IES at the duodenum and IES at the ileum on neuronal activities of the VMH; 3) to better understand if the neuronal activity modulated by IES was mediated via the vagal pathway. Methods Extracellular potentials of neurons in the VMH were recorded in 18 anesthetized rats. IES at the duodenum or ileum was performed in duodenal-distention responsive (DD-R) neurons with 3 sets of parameters (IES-1 with trains of short-pulses: 4mA, 2s-on, 3s-off, 2ms, 20Hz; IES-2 with long-pulses: 6mA, 20cpm, 100ms; IES-3, same as IES-1 but 40Hz). Results IES-1 at the duodenum and the ileum activated 70.6% and 73.3% of the DD-R neurons, respectively; Similar percentages of the neurons were activated with IES-3 at the duodenum and the ileum (70.6% vs. 66.7% P=0.91), respectively. IES-2 at these locations activated only 25% and 46.2% of the DD-R neurons, respectively (P>0.05). IES at the duodenum with parameter set, IES-1 or IES-3 was significantly more potent than the parameter set, IES-2 (neuronal activation: 70.6% vs. 25%, P<0.05). Bilateral vagotomy only partially blocked the effects of IES on the neuronal activity in the VMH, indicating that extra-vagal pathways can mediate these effects. Conclusions IES with different parameters activates 25–70.6% of the VMH neurons responsive to DD, and IES with trains of short-pulses seems more effective than IES with long-pulses. The vagal pathway and extra-vagal pathways are involved in the modulatory effects of IES on the central neurons in the satiety center.

A Potential and Novel Therapy for Obesity: “Appendix” Electrical Stimulation in Dogs

“…The increase in satiety would lead to a reduction in food intake and subsequent weight loss. This central neuronal mechanism was demonstrated with GES [42] and DES [43] and also implicated in our preliminary study (unpublished data).…”

Inhibitory effects of intestinal electrical stimulation on food intake, weight loss and gastric emptying in rats

“…In one previous study, IES was reported to activate the neurons in the nucleus tractus solitarii, suggesting a vagal afferent pathway (23). In a more recent study, IES was found to activate the neurons in the ventromedial nucleus, which is related to satiety (29).…”

Pulse Width-Dependent Effects of Intestinal Electrical Stimulation for Obesity: Role of Gastrointestinal Motility and Hormones

“…Compared to sham IES which only slightly increased GLP-1 secretion at 15 min after oral glucose, IES of both 0.3 and 3 ms significantly enhanced the secretion of GLP-1. IES was reported to modulate neuronal activities in the nucleus of the solitary tract and hypothalamus in rats via the activation of vagal afferent pathway [29,30]. This rapid rise in GLP-1 secretion which was augmented by IES may be mediated indirectly through a neuro/endocrine pathway, rather than through forwarding the nutrient for the direct interactions of the luminal contents with L cells [31].…”