Study On Regulation Of Discharge Activity And Gastric Motility Of Gastric Distraction Sensitive Neurons By DVC - PVN Nesfatin - 1 Pathway

Objective:Nesfatin-1 as a peptide can regulate gut motor function, but the underlying mechanisms have yet to be elucidated.The study aimed to illustrate the formation between the DVC and PVN nesfatin-1 pathway and to explore the effects of nesfatin-1 in PVN on gastric distension-sensitive neurons and the regulation by the DVC.Methods:①Retrograde tracing were used to determine neuronal projections. ②Fluorescent-immunohistochemistry were used to determine NUCB2/nesfatin-1 neuronal projections. ③The nuclei microinjection and nuclei electrical stimulation, extracellular discharges of single unit neuron were used to observe the effects of nesfatin-1 on the GD neurons. ④Gastric motility recording in vivo were used to monitor the effects of nesfatin-1 on the amplitude of constriction and frequency of gastric motility in conscious rats. ⑤Gastric motility recording in vivo were used to monitor the effects of nesfatin-1 on the amplitude o f constriction and frequency of gastric motility in rats with the vagus nerve to be cut off.Results:①NUCB2/Nesfatin-1/fluorogold-double labeled neurons were detected in the PVN. ②Of 187 recorded neurons in PVN,126 neurons were GD responsive neurons. Injection of nesfatin-1 could excited GD-E neurons(P<0.01), and inhibit GD-I neurons(P<0.01). ③Injection of mixture of nesfatin-1 and SHU9119 could weake n the responses induced by nesfaton-1(P<0.05). Out of GD-E neurons in the PVN, 24 were inhibited by electrical stimulation of the DVC, 14 were excited and 33 had no response. O ut of GD-I neurons in the PVN, 16 were inhibited by electrical stimulation of the DVC, 13 were excited and 26 had no response. Pretreatment with anti-NUCB2/nesfatin-1 antibody in the PVN could further decrease the firing rate of most of the GD- E neurons(P<0.01) and increase the firing rate of most of the GD-I neurons(P < 0.01). ④ Gastric motility recording in vivo shoe that injection of nesfatin-1 in PVN, can decreased the amplitude and frequency(P<0.01), SHU9119 could weaken the responses induced by nesfaton-1(P<0.05). ⑤Cut off the vagus nerve could weaken the responses induced by nesfaton-1(P<0.05).Conclusion:Nesfatin-1 could inhibitory gastric motility in PVN via melanocortin pathway and influence the firing activity of GD neurons.