Effect of Orexin-A on Glucose Sensitive Neurons in the Hypothalamus of Rats

Author(s): Mengling Zhang, Xiangrong Sun, Feifei Guo, Shengli Gao, Yanling Gong, Luo Xu

Orexin-A is an excitatory neuropeptide that mainly located in the lateral hypothalamus(LHA). Orexin-A can regulates multiple physiological activity that include arousal, wakefulness and appetite. We aim to discuss the effects of orexin-A on the glucose sensitive neurons in the hypothalamus, in order to make further investigation of potential mechanisms in the appetite system. Cerebral stereotaxic technique was used to inject orexin-A and glucose into nucleus accumbens of rats. Extracellular single unit discharges were used to observe the activity of glucose sensitive neurons in the nucleus accumbens of rats. Sixty-eight glucose sensitive neurons were recorded after microinjection of glucose into nucleus accumbens. Based on different sensitive reactivity, the discharge frequency of forty-two neurons were increased (defined as glucose excitatory neuron) and twenty neurons were decreased (defined as glucose inhibitory neuron). The discharge frequency of thirty neurons were increased in the glucose excitatory neurons after administration of orexin-A through four-barrel glass microelectrode. The discharge frequency of fifteen neurons were increased in the glucose inhibitory neurons after administration of orexin-A through four-barrel glass microelectrode. The effect of orexin-A on turning the discharge frequency of glucose sensitive neurons was abolished by orexin-A receptor antagonists SB-334867. The change of discharge frequency of glucose sensitive neurons did not have significant difference after injection of saline through three-barrel glass microelectrode. It is suggested that orexin-A can regulate glucose sensitive neurons in nucleus accumbens, which may be parts of mechanism of the regulation of food intake.

orexin-A, feeding, glucose sensitive neuron

1. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behaviour. Cell, 1998; 92(4):573-85.
2. De Lecea L, Kilduff TS, Peyron C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci, 1988; 95(1):322-27.
3. Petrovich GD, Hobin MP, Reppucci CJ. Selective Fos induction in hypothalamic orexin/hypocretin, but not melanin-concentrating hormone neurons, by a learned food-cue that stimulates feeding in sated rats. Neuroscience, 2012; 224: 70–80.
4. Nixon JP, Mavanji V, Butterick TA, et al. Sleep disorders, obesity, and aging: the role of orexin. Ageing Res Rev, 2015; 20:63–73.
5. Hu B, Yang N, Qiao QC, et al. Roles of the orexin system incentral motor control. Neurosci Biobehav Rev, 2015; 49: 43–54.
6. Shu Sun, Luo Xu, Xiangrong Sun, et al. Orexin-A affects gastric distention sensitive neurons in thehippocampus and gastric motility and regulation by the perifornicalarea in rats. Neuroscience Research. doi: 10.1016/j.neures. 2016.04.001.
7. Mayannavar S, Rashmi KS, Rao YD, et al. Effect of Orexin-A infusion in to the Nucleus Accumbens on consummatory behaviour and alcohol preference in male Wistar rats. Indian J Physiol Pharmacol, 2014; 58(4):319-26.
8. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. Academic Press Inc, San Diego, CA, 2007.
9. Trudel L, Tomasetto C, Rio MC, et al. Ghrelin/motilin-related peptide is a potent prokinetic to reverse gas-tric postoperative ileus in rat. Am J Physiol, 2002; 282:G948-52.
10. WANG W G, CHEN X, JIANG H, et a1. Effects of ghrelin on glucose-sensing and gastric distension sensitive neurons in rat dorsal vagal complex[J]. Regul Pept，2008，146(1-3):169-175．
11. Levin BE, Ambrose ADM, Vanessa HR. Brain glucose sensing and body energy homeostasis：role in obesity and diabetes．Am J Physiol Regul Integr Comp Physiol, 1999; 276:1223-31.
12. ROUTH V H. Glucose-sensing neurons: are they physiologically relevant[J]? Physiol Behav, 2002; 76:403-41.
13. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature, 1998; 395:763-770.
14. Schwartz MW , Woods SC, Pone D Jr, et a1. Central nervous system control of food intake. Nature, 2000; 404:661- 671.