Energy Supply And Demand Mandarin Vole Adaptive Changes In Hypothalamic Npy, Pam And Digestive Tract Of Nos

There is a complex physiological regulating system in organism which can balance energy intake and comsume,so that body weight and fat content maintain in a relatively stable level.It has been demonstrated that both central never system(CNS) and peripheral nervous system (PNS) participate in energy balance.Hypothalamus which is a relatively advanced central nervous system plays an important role in the regulation of food intake and energy balance.Recent research has identified the existence of an appetite regulation network(ARN) network in the hypothalamus involved in the regulation of daily food intake,which can produce many orexigenic and anorexigenic peptides.Neuropeptide Y(NPY) is a primary orexigenic signal within this network, which appears to be an important peptide for the action of in the regulation of food intake.NPY is mainly distributed in the arcuate nucleus(ARC),paraventricular nucleus(PVN),ventromedial nucles (VMH),dorsomedial nucleus(DMH) of the hypothalamus and lateral hypothalamus(LH); therefore,it is believed that there is a complicated NPY-Network in hypothalamus,and ARC-PVN axis plays important role in energy balance.In the hypothalamus,NPY is synthesized primarily in the ARC and from there it is transported to terminals via axonal transportation from which it is released primarily in the PVN.Higher NPY and NPY mMRA density were observed in states of food deprivation or increased energy demands such as starvation,diabetes,,cold enviroment,obesity, intense exercise,pregnancy and lactation.Central administration of NPY causes remarkable increase of food consumption and there was good linearity relationship between increased food intake and NPY dosage in certain extent;while inhibition of appetite by continuous intraventricular infusion of NPY antisense oligodeoxynucleotides or antagonist of NPY suppresses food intake.PAM was discovered more than 20 years ago in the seminal studies of Eipper and is a post-translational processing enzyme which catalyzes the hydroxylation of the C-terminal glycine in a large number of inactive neuropeptides and is responsible for the posttranslational modification of many important neuropeptides.PAM is a rate limiting step in the biosynthesis of NPY and many other neuropeptides,which is the only enzyme that catalyzes peptide amidation modification.Repeated electroconvulsive shock increased amounts of NPY and PAM in mossy fibers, and dentate granule cell dendrites contained increased amounts of NPY,PAM.However effects of PAM on feeding behavior has not been evaluated.Repeated electroconvulsive shock increased amounts of NPY and PAM in mossy fibers,and dentate granule cell dendrites contained increased amounts of NPY,PAM,However effects of PAM on feeding behavior has not been evaluated, The morphological and structural changes of digestive tract is an important adaptive strategy. Research shows that feeding habit is the main cause of different morphological and structural of digestive tract within interspecies and the differences mainly display in length of digestive tract;while intraspecific difference closely relates with food quality and energy demands. Gastroenteric activity is dominated both by autonomic nerve and extrinsic nerve plexus,therefore regulation of gastroenteric activity is a very complex process,nitric oxide(NO) is one of nonadrenergic noncholinergic(NANC) neurotransmitters which exhibit a wide range of biologic functions including inhibiting contraction of smooth muscles,affecting basal tension of mucosal blood vessels,increasing volume of mucosal blood flow and mucosal thickness,and regulating secretion of gastric mucus.To investigate CNS's adaptation mechanism in digestion and absorption under different energy demands and supplies,and discuss regulating relationship between central never system(CNS) and peripheral nervous system(PNS),We used the mandarin vole Microtus mandarinus as the animal model.In our study,immunohistochemisty and NADPH-NDP histochemistry were employed to test the expression of hypothalamic neuropeptide Y(NPY),its rate-limiting enzyme -Peptidylglycineα-amidating monooxygenase(PAM) in hypothalamus and the distribution of nitric oxide synthase (NOS) in gastrointestinal myenteric plexus among non-Lactating female,lactating female and fasting female.Furthermore,the effects of intra- cerebroventricular(icv 8ug/ul) microinjection of NPY on the distribution of NOS in gastrointestinal myenteric plexus were also observed.Results were as follows1.positive immunohistochemical spots of NPY and PAM were mainly distributed in regions of arcuate nucleus(ARC),paraventricular nucleus(PVN),ventromedial nucles(VMH),dorsomedial nucleus(DMH) of hypothalamus;2.hypothalamic positive NPY spots in lactating females and fasting females ascended significantly compared with non-lactating females,and positive PAM spots in ARC and PVN of fasting females significantly elevated compared with non-lactating females and lactating females,so did NPY microinjected females compared with saline microinjected females;3.higher levels of NOS positive ganglions and neurons were observed in gastric and duodenum in myenteric plexus of lactating females and fasting females in comparison with non-lactating females,and NPY microinjected females presented the same changes compared with saline microinjected females;4.Both NOS positive ganglions,neurons in jejunum of lactating females compared with non-lactating females and microinjected NPY females compared with microinjected saline females were higher;5.Number of NOS positive neurons in every NOS positive ganglions in Cecum of lactating females were more that of non-lactating females;while NOS positive ganglions and positive neurons of NPY-injected females were more compared with saline-injected females.6.Higher level of NOS positive ganglions were observed in myenteric plexus of Ileum of lactating females in comparison with non-lactating females.7.Food consumption were prominently increased by icy injection of NPY.We conclude that:both CNS and PNS take part in gastrointestinal adaptive regulation to settle higher energy demands and supply-demand contradiction in energy,and the adaptation mechanism are varied under different energy threatening.Our results also suggest that NPY in hypothalamus is an important regulating peptide,functioning not only directly via enhancing food intake and digestive efficiency to meet the requirements of nutrition and energy,but also via regulating distribution of NOS neurons in digestive tract to modulate digestion.However,the contradiction of energy intake and expenditure is escalated by fasting,both expression of NPY and PAM were increased suggest that biological activity is also a important strategy under severe energy threatening.