| Objective: Nesfatin-1 is an 82-amino acid anorexia peptide with expression of nesfatin-1 immunopositive neurons in the arcuate nucleus(ARC).Both PVN and ARC are important nuclei that regulate feeding and gastrointestinal motility,and there is a round-trip fiber connection between the two nuclei.However,whether nesfatin-1 is involved in gastric motility and gastric acid secretion regulation in the ARC-PVN pathway remains unclear.The purpose of this study was to investigate whether there is a neuronal or functional pathway of nesfatin-1 between ARC-PVN,and whether this pathway is involved in gastric afferent information,gastric motility,gastric acid secretion and other functional regulation.Methods: 1.Using fluorescent gold retrograde tracing combined with fluorescent immunohistochemistry to observe the composition of ARC-PVN nesfatin-1 neural pathway;2.Single-cell electrophysiological studies showed that 182 GD neurons were recorded in PVN,of which 116 neurons were gastric dilatation-excited neurons(GD-E)and 44 neurons were gastric dilatation-suppressing neurons(GD-I),suggesting that PVN can accept incoming information from the stomach.3.The effects of nesfatin-1 on gastric acid secretion and gastric motility in rats in ARC-PVN pathway and its potential mechanisms were observed by microinjection of nucleus,nuclear stimulation,gastric acid and body motion measurement.Results: 1.Fluorescent gold retrograde tracking combined with fluorescence immunohistochemistry showed that there was nerve fiber connection between ARC-PVN,and fluorescent gold(FG)in ARC coexisted with nesfatin-1 immunopositive neurons,suggesting that nesfatin-1 immunoreactive nerve in ARC The element can emit nerve fibers that are projected to the PVN.2.Single-cell electrophysiological studies showed that 182 GD neurons were recorded in PVN,of which 116 neurons were gastric dilatation-excited neurons(GD-E)and 44 neurons were gastric dilatation-suppressing neurons(GD-I),suggesting that PVN can accept incoming information from the stomach.3.Microinjection of MCH into PVN.In 116 GD-E neurons,71 neurons(71/116,61.21%)had significantly higher discharge frequency(P<0.05),and 35 neurons had significant discharge frequency.Decrease(P<0.05).Among the 66 GD-I neurons,37 neurons(37/66,56.06%)showed a significant decrease in discharge activity(P<0.05),and 11 neurons had significantly increased discharge frequency(P<0.05).4.PVN microinjection of nesfatin-1,in 71 MCH-excitability/GD-E neurons,44 neurons(44/71,61.97 %)showed significant decrease in discharge activity(P<0.05),15 nerves The discharge activity of the element(15/71,21.12 %)was significantly enhanced(P<0.05).Among the 35 MCH-inhibitory/GD-E neurons,16 neurons(16/35,45.71%)showed significant increase in discharge activity(P<0.05),and 7 neurons(7/35,20.00 %)discharge activity was significantly reduced(P<0.05);nasfatin-1 was injected in PVN,and 21 neurons(21/37,56.75 %)were discharged in 35 MCH-excitatory/GD-I neurons significantly(P < 0.05).9 neurons(9 / 37,24.32 %)significantly reduced discharge activity(P<0.05).Among the 11 MCH-inhibitory/GD-E neurons,the discharge activity of 3 neurons(3/11,27.27 %)was significantly enhanced(P<0.05),and the discharge activity of 6 neurons(6/11,54.55 %)was significantly attenuated(P<0.05);and the effect of nesfatin-1 on MCH-reactive/GD neuron discharge activity was partially blocked by the MCHR1 receptor antagonist PMC-3881-PI.It is suggested that nesfatin-1 can regulate the discharge activity of MCH-reactive/GD neurons in PVN,and this effect may pass through the MCHR1 receptor signaling pathway.5.Electrical stimulation of ARC can cause 85.71%(42/49)nesfatin-1-inhibitory/MCH-excitability/GD-E neuron excitation,and its discharge frequency increases from 3.06±0.97 Hz to 9.87 ± 2.44 Hz(P<0.05).Electrical stimulation of ARC inhibited the discharge activity of 10.20 %(5/49)nesfatin-1-inhibitory/MCH-excitability/GD-E neurons(P<0.05),but there were two other nesfatin-1-inhibitions.There was no significant change in MCH-excitability/GD-E(2/49,4.08 %)discharge activity(P>0.05).Electrical stimulation of ARC stimulated 31 nesfatin-1-inhibitory/MCH-inhibitory/GD-I neurons(31/36,86.11 %)discharge activity,and its discharge frequency increased from 2.96±0.88 Hz to 8.76±2.05 Hz(P<0.05),and inhibited 4 nesfatin-1-inhibitory/MCH-inhibitory/GD-I neurons(4/36,11.11 %) discharge(P<0.05),and one neuron(1/ 36,2.78 %)The discharge frequency did not change significantly(P>0.05).Pre-injection of the-nesffatin-1 antibody into PVN partially blocked electrical stimulation of ARC-induced changes in cell discharge.It is suggested that nesfatin-1 in the ARC-PVN pathway may be involved in the regulation of excitatory activities of MCH/GD neurons.6.PVN microinjection of nesfatin-1 significantly attenuated gastric motility or gastric acid secretion in rats(P<0.05-0.01).However,PVN injection of PMC-3881-PI significantly attenuated sfatin-1 on gastric motility or gastric acid secretion in rats.Inhibition effect(P<0.05-0.01).After electrical stimulation of ARC,the gastric contraction amplitude and contraction frequency were significantly increased(P<0.05-0.01),and gastric acid secretion was significantly increased(P<0.05-0.01).However,if PVN was pre-injected with PMC-3881-PI or nesfatin-1 antibody,this first stimulatory effect induced by electrical stimulation was significantly attenuated(P < 0.05).Conclusion: There is a nesfafin-1 neural and functional pathway between ARC-PVN;this pathway can receive information from the gastric distraction,and can send out impulses to participate in neuronal excitability,gastric motility,and regulation of gastric acid secretion,and melanin-concentrating hormones may Also involved in the regulation process.. |
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