Study On The Constitution Of LHA-PVN Nesfatin-1 Pathway In Hypothalamus And Its Regulation On Gastric Motility

Objective: To study the neural pathway and the functional pathway of nesfatin-1 in the lateral hypothalamic area and the paraventricular nucleus(LHA-PVN),To investigate the mechanism and potential mechanism of nesfatin-1 in gastric afferent information and gastric motility in this pathway.Methods: Using Fluorogold(FG)retrograde tracing combined with immunohistochemistry staining,observe the structure of LHA-PVN nesfatin-1 pathway;The effects of nesfatin-1 on the activity of GD neurons in PVN were recorded by extracellular discharge recordings;The effects of nesfatin-1 in LHA-PVN pathway on the activity of GD neurons were observed by electrical stimulation of LHA and microinjection of nesfatin-1 antibody into PVN;The effects of nesfatin-1 in PVN on gastric motility and gastric emptying were observed by in vivo gastric motility recordings;LHA was stimulated and PVN was injected with nesfatin-1 antibody to observe the regulation and mechanism of nesfatin-1 on gastric motility in LHA-PVN pathway.Results:(1)Fluorogold retrograde tracing combined with fluorescence immunohistochemistry assay showed that PVN injection of fluorescent gold in 7 days,In LHA,neurons with fluorescent gold labeling were observed,In combination with nesfatin-1 immunofluorescence staining,nesfatin-1 immunoreactive positive expression was found in the neurons of LHA partially labeled with fluorescent gold under microscope.It is suggested that some nesfatin-1 neurons in LHA may send fibers to PVN.(2)PVN microinjection of nesfatin-1,frequency of GD-E neurons decreased significantly(P<0.05),but the frequency of GD-I neurons increased significantly(P < 0.05);if PVN is pre injected of oxytocin receptor antagonist H4928,the nesfatin-1 effect on GD neurons significantly decreased(P < 0.05).It is suggested that nesfatin-1 may participate in the regulation of gastric afferent information in hypothalamus PVN,and this effect may be related to the signal pathway of oxytocin receptor.(3)Electrical stimulation of LHA,frequency of GD-E and GD-I neurons in the PVN increased significantly(P<0.05);if PVN is pre injected with anti NUCB2/nesfatin-1antibody,then electrically stimulated LHA,the discharge activities promote GD-E neurons induced by stimulation of the power to further strengthen(P<0.05),while GD-I neurons discharge activity decreased(P<0.05).These findings suggest that the LHA-PVN nesfatin-1 pathway may be involved in the regulation of gastric afferent information.(4)PVN microinjection of nesfatin-1 and gastric motility in rats was decreased significantly(P<0.05),gastric emptying rate decreased significantly(P<0.05);If PVN was injected H4928 in advance,the gastric motility and gastric emptying effect(P<0.05)could be significantly reduced by nesfatin-1.It is suggested that nesfatin-1 may participate in the regulation of gastric motility in hypothalamus PVN,and this effect may also be related to the oxytocin receptor pathway.(5)Electrical stimulation of LHA,gastric motility index in rats increased significantly(P<0.05).if PVN was injected with anti NUCB2/nesfatin-1 antibody and stimulated LHA again,the effect of gastric motility induced by electrical stimulation was further enhanced(P<0.05).These findings suggest that the LHA-PVN nesfatin-1 pathway may be involved in the regulation of efferent gastric motility.Conclusion: There is a nesfatin-1 nerve and functional pathway between LHA and PVN.This pathway is involved in the regulation of gastric afferent information and efferent gastric motility,and the signal of oxytocin receptor may be involved in the regulation of this process.