The Effects ofNesfatin-1 in the Paraventricular Nucleus on Gastric Motility and Its Potential Regulation by the Lateral Hypothalamic Area in Rats / 现代生物医学进展

ABSTRACT

Objective:The current study investigated the effects of nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) on gastric motility and the regulation of the lateral hypothalamic area (LHA).Methods:The projection of nerve ?ber and expression of nesfatin-1 were observed by retrograde tracing and fluo-immunohistochemistry staining;The 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;Gastric 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.Results:Nesfatin-1 inhibited the majority of the GD-E neurons(1.97± 0.12 Hz vs.1.15± 0.07 Hz) and excited GD-I neurons (1.74± 0.10 Hz vs.3.04± 0.18 Hz) in the PVN,which were weakened by oxytocin receptor antagonist H4928 (GD-E1.38± 0.08 Hz,P＜0.05 vs.nesfatin-1;GD-I2.49± 0.15 Hz,P＜0.05 vs.nesfatin-1).Gastric motility experiments showed that administration ofnesfatin-1 in the PVN decreased gastric motility.Retrograde tracing and immunofluorescent staining showed that nucleobindin-2/nesfatin-1 and fluorogold double-labeled neurons were observed in the LHA.Electrical LHA stimulation excited the firing rate of GD-responsive neurons (GD-E2.06± 0.12 Hz vs.4.23± 0.21 Hz,GD-I1.61± 0.09 Hz vs.4.83± 0.25 Hz) in the PVN.Pre-administration of an antinucleobindin-2/nesfatin-1 antibody in the PVN strengthened gastric motility,decreased GD-E neurons (1.74± 0.10 Hz vs.3.04± 0.18 Hz) and excited the discharging of the GD-I neurons(4.15± 0.18 Hz vs.4.83± 0.25) induced by electrical stimulation of the LHA.Conclusion:Nesfatin-1 in the PVN could serve as an inhibitory factor to inhibit gastric motility,which might be regulated by the LHA.