| Objective: to observe the formation between the central nucleus of the amygdala(CNA)and the dorsal motor nucleus of the vagus(DMV)nesfatin-1 neuronal pathway;to explore the effects of nesfatin-1 on gastric distention(GD)sensitive neurons in the CNA and gastric motility in rats;and the potential regulation mechanisms by DMV.Methods: 246 adult male Wistar rats were used.Retrograde tracing combing with immunohistochemistry staining were used to observe the CNA-DMV nesfatin-1 neuronal pathways.Electrophysiological study were used to identify the GD sensitive neurons in the CNA,and to record the changes of neuronal discharge after injection of nesfatin-1 or melanocortin 3/4 receptors antagonist SHU9119;Stimulating DMV were used to study the influence and potential regulation mechanisms of DMV on the effect of CNA nesfatin-1;CNA microinjected of different concentration of nesfatin-1 to observe the effect of CNA nesfatin-1 on gastric contraction amplitude and frequency in rats,and subdiaphragmatic vagotomy was done to discuss this mechanism.Results: 1 Nesfatin-1/ fluorogold(FG)dual labelled neurons were detected in CNA after injection of FG into DMV for 7 days,which indicates that some of the nesfatin-1-immunoreactive neurons arising from DMV may project to CNA.2 43 of 62(43/62,69.4%)GD-E neurons in the CNA were activated by nesfatin-1,with firing rate increased from 2.45±0.62 Hz to 3.52±1.07Hz(t =2.74,P<0.05).30 of 42(30/42,71.4%)GD-I neurons were inhibited by nesfatin-1,resulting in a significant decrease in the firing rate from 1.57±0.64 Hz to 0.89±0.39Hz(t =2.87,P<0.05).The nesfatin-1-induced responses were partially abolished by the pretreatment with melanocortin 3/4 receptors antagonist SHU9119.3 78% nesfatin-1-excited GD-E neurons were further excited by electrical stimulation of DMV with the firing rate markedly raised from 3.37±1.02 Hz to 4.65±1.13Hz(t=2.66,P<0.05).77.1% nesfatin-1-inhibited GD-I neurons were also excited by electrical stimulation of the DMV with the firing rate raised from 1.54±0.43 Hz to 2.36±0.82Hz(t=2.8,P<0.05).Anti-NUCB2/nesfatin-1 antibody was pre-administrated into CNA followed by electrical stimulation of DMV.It showed that the firing rate of 60.9% nesfatin-1-responsive GD-E neurons were significantly decreased in the CNA(4.24± 1.25 Hz vs.3.08 ± 0.79 Hz,t=2.48,P<0.05),but increased for 62.2% nesfatin-1-responsive GD-I neurons(2.30±0.85 Hz vs.3.25±1.02 Hz,t=2.26,P<0.05).4 Nesfatin-1 administered to the CNA dose-dependently decreased the amplitude and frequency of the gastric motility(P<0.05~0.01).Pretreatment with SHU9119 partially blocked the effects of nesfatin-1.5 Pretreatment of subdiaphragmatic vagotomy could abolish the diminished gastric contractions induced by CNA injection of nesfatin-1.Conclusions: These findings suggest that nesfatin-1 may regulate the activity of GD sensitive neurons and gastric motility via the melanocortin pathway in CNA and the CNA-DMV-vagus-gastrointestinal pathway may be involved in this potential mechanism. |
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