neuropeptide-y and Dehydration

Food-restricted animals present metabolic adaptations that facilitate food-seeking behavior and decelerate energy utilization by reducing the hypothalamus-pituitary-thyroid (HPT) axis function. Stress by dehydration induces an anorexic behavior in rats, loss of weight and reduced food intake when compared to ad libitum fed animals, however these alterations are accompanied by HPT axis changes such as increased serum thyrotropin levels and enhanced expression of thyrotropin-releasing hormone (TRH) in the paraventricular nucleus of the hypothalamus, which is considered as anorexigenic peptide. In contrast, a pair-fed group conformed by forced-food-restricted animals (FFR) (eating the exact same amount of food as dehydration-induced anorexic rats--DIA rats) present decreased TRH mRNA levels. NPY synthesis in the arcuate nucleus and orexin-expressing neurons from the lateral hypothalamic area (LHA) are activated during food restriction. These brain structures project into PVN, suggesting that NPY and orexins are possible factors involved in TRHergic neuron activation in DIA rats. Leptin signaling is another likely factor to be involved in TRH differential expression. Therefore, to gain more insight into the regulation of the feeding behavior in the experimental models, we analyzed Y1, Y5, Ox1-R and Ob-R(b) mRNA levels in PVN and prepro-orexin in LHA, since their signaling to the PVN might be altering TRH synthesis and feeding in DIA animals. Prepro-orexinergic cells were activated in FFR animals; Ox1-R and Y1 expression was reduced in FFR vs. controls or DIA group. Compensatory changes in PVN receptor expression of some feeding-related peptides in anorexic rats may alter TRHergic neural response to energy demands.

Topics: Animals; Anorexia; Dehydration; Feeding Behavior; Gene Expression Regulation; Hypothalamo-Hypophyseal System; Intracellular Signaling Peptides and Proteins; Leptin; Male; Malnutrition; Neurons; Neuropeptide Y; Neuropeptides; Orexin Receptors; Orexins; Paraventricular Hypothalamic Nucleus; Pituitary-Adrenal System; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Neuropeptide Y; Signal Transduction; Thyrotropin; Thyrotropin-Releasing Hormone

Anorexia that accompanies cellular dehydration in rats (DE-anorexia) offers a relatively simple model for investigating the functional organization of neural mechanisms that can suppress feeding during dehydration. Previous studies strongly suggest that the inputs that drive ingestive behavior control neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) remain active during DE-anorexia. Here we examine whether these two regions retain their sensitivity to neuropeptide Y (NPY). NPY is an important component in two major feeding-related inputs from the arcuate nucleus and the hindbrain. We found that intake responses to NPY injections in the LHA and PVH were suppressed in DE-anorexia, but the PVH remained less sensitive to the effects of NPY than the LHA in DE-anorexic animals. Indeed the higher dose of NPY (238 pmol) completely overcame shorter periods of DE-anorexia when injected into the LHA but not the PVH. However, the latency to eat after NPY injections remained unchanged from control animals, regardless of NPY dose, injection location, or intensity of anorexia. Furthermore, the onset and size of the strong and rapidly induced compensatory feeding that follows the return of water to DE-anorexic animals was also unaffected by any NPY injections. These data support the hypothesis that DE-anorexia develops as a consequence of the premature termination of regularly initiated meals, which perhaps involves processes that alter the sensitivity of satiety mechanisms downstream to the PVH and LHA.

Topics: Animals; Anorexia; Dehydration; Disease Models, Animal; Drinking; Drinking Behavior; Eating; Feeding Behavior; Hypothalamic Area, Lateral; Injections; Male; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Reaction Time; Satiety Response; Time Factors

Localization of neuropeptide Y (NPY) mRNA in the hypothalamus of chickens was studied by in situ hybridization with digoxigenin-labeled chicken NPY cRNA probe. The largest number of perikarya-expressing NPY mRNA was found within the mediobasal hypothalamus, including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence. Many NPY perikarya were noted to surround the nucleus rotundus and to be present in the supraoptic nucleus. Moreover, some perikarya were detected in the nucleus of basal optic root, bed nucleus pallial commissure, and nucleus striae terminalis close to the lateral forebrain bundle. NPY-immunoreactive nerve fibers were densely distributed in these regions containing the NPY mRNA-expressing perikarya. Following food deprivation for four days, perikarya-expressing NPY mRNA and peptide were markedly increased in the mediobasal hypothalamus and particularly so in the infundibular nucleus. No changes, however, were detected in other regions containing NPY-positive perikarya. Water deprivation induced less increase in NPY-positive perikarya in the mediobasal hypothalamus compared to food deprivation. After gonadectomy, the number of NPY-positive perikarya in the mediobasal hypothalamus was unaltered. Northern blot analysis with (32)P-labeled chicken NPY cDNA probe demonstrated that a 2.7-fold increase of NPY mRNA was induced by starvation and a 1.5-fold increase was induced by dehydration, whereas the NPY mRNA band remained unchanged after gonadectomy. Thus, it seems that NPY neurons located in the mediobasal hypothalamus are involved in feeding behavior but not reproductive activity.

Topics: Animals; Blotting, Northern; Chickens; Dehydration; Food Deprivation; Hypothalamus; Image Processing, Computer-Assisted; Immunohistochemistry; In Situ Hybridization; Male; Neuropeptide Y; Orchiectomy; RNA, Messenger

We have investigated the hormonal and hypothalamic neuropeptidergic substrates of dehydration-associated anorexia. In situ hybridization and hormone analyses of anorexic and paired food-restricted rats revealed two distinct profiles. First, both groups had the characteristic gene expression and endocrine signatures usually associated with starvation: increased neuropeptide Y and decreased proopiomelanocortin and neurotensin mRNAs in the arcuate nucleus (ARH); increased circulating glucocorticoid but reduced leptin and insulin. Dehydrated animals are strongly anorexic despite these attributes, showing that the output of leptin- and insulin-sensitive ARH neurons that ordinarily stimulate eating must be inhibited. The second pattern occurred only in anorexic animals and had two components: (1) reduced corticotropin-releasing hormone (CRH) mRNA in the neuroendocrine paraventricular nucleus (PVH) and (2) increased CRH and neurotensin mRNAs in the lateral hypothalamic (LHA) and retrochiasmatic areas. However, neither corticosterone nor suppressed PVH CRH gene expression is required for anorexia after dehydration because PVH CRH mRNA in dehydrated adrenalectomized animals is unchanged from euhydrated adrenalectomized controls. We also showed that LHA CRH mRNA was strongly correlated with the intensity of anorexia, increased LHA CRH gene expression preceded the onset of anorexia, and dehydrated adrenalectomized animals (which also develop anorexia) had elevated LHA CRH gene expression with a distribution pattern similar to intact animals. Finally, we identified specific efferents from the CRH-containing region of the LHA to the PVH, thereby providing a neuroanatomical framework for the integration by the PVH of neuropeptidergic signals from the ARH and the LHA. Together, these observations suggest that CRH and neurotensin neurons in the LHA constitute a novel anatomical substrate for their well known anorexic effects.

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Animals; Anorexia; Arcuate Nucleus of Hypothalamus; Axonal Transport; Body Weight; Corticosterone; Corticotropin-Releasing Hormone; Dehydration; Food Deprivation; Gene Expression Regulation; Hypothalamic Area, Lateral; Insulin; Leptin; Male; Neuropeptide Y; Neuropeptides; Neurotensin; Paraventricular Hypothalamic Nucleus; Phytohemagglutinins; Pro-Opiomelanocortin; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thymus Gland; Time Factors; Transcription, Genetic

The role of neuropeptide Y (NPY) in the central control of appetite and energy balance is now established, but its involvement in the control of drinking and fluid homeostasis is less well characterized. Central administration of NPY stimulates drinking in rats, an effect believed to be independent of its orexigenic effects. Recent studies have demonstrated increased preproneuropeptide Y (preproNPY) mRNA in the arcuate nucleus (ARC) of the rat following food deprivation (FD) or water deprivation (WD). Because WD also suppresses food intake, it was not clear whether the osmotic or the anorectic effects of this stimulus were responsible for increased ARC preproNPY mRNA. In an attempt to distinguish between these possibilities, the present study further examined the effects of hyperosmotic stimuli on preproNPY mRNA in the ARC. Salt loading (4 or 7 days) and WD (4 days) both increased the abundance of preproNPY mRNA in the ARC. These increases were proportional to the severity and duration of treatment and were related to the degree of anorexia and weight loss. In a separate study WD, FD, or combined food and water deprivation (4 days) all produced similar decreases in body weight, but WD produced a smaller increase in ARC preproNPY mRNA. All of these treatments resulted in the appearance of NPY-like immunoreactivity in ARC neuronal perikarya. Together these findings suggest that NPY neuron activity in the ARC may be regulated by decreases in food intake rather than changes in body weight per se or increased osmolarity and support other data implicating NPY in the central regulation of energy homeostasis.

Topics: Animals; Anorexia; Arcuate Nucleus of Hypothalamus; Dehydration; Food Deprivation; Immunohistochemistry; In Situ Hybridization; Male; Neuropeptide Y; Osmosis; Protein Precursors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Water Deprivation

The magnocellular hypothalamo-neurohypophysial system is, via a release of vasopressin from nerve terminals in the neurohypophysis to the peripheral blood, centrally involved in the regulation of body salt and water homeostasis. Furthermore, it has been shown that expression of neuropeptides co-existing with vasopressin or oxytocin in magnocellular neurons is influenced by salt loading. We here report, that neuropeptide Y (NPY)-immunoreactivity, which is normally not observed in the magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei of rats becomes immunohistochemically detectable after salt loading. Using a double-immunohistochemical procedure on the same brain sections, it is shown that NPY is co-existing with either vasopressin or oxytocin in these neurons. Within the neurohypophysis of normal rats, a moderate number of predominantly fine calibered NPY-immunoreactive nerve fibers most often coursing along vessels is observed in addition to a low number of large peptidergic terminals. In salt-loaded rats, however, the number of NPY-immunoreactive neurohypophysial large nerve terminals in apposition to vascular lumina is drastically increased. By using quantitative receptor autoradiography, it is demonstrated that in salt-loaded animals, the number of neurohypophysial NPY binding sites is decreased to nearly undetectable levels (0.054 +/- 0.02 fmol/mg) compared to a very high density of binding sites in normal animals (1.151 +/- 0.15 fmol/mg). This raises evidence that NPY containing hypothalamo-neurohypophysial neurons as well as peripherally released NPY may be involved in the regulation of water homeostasis via NPY receptors in the neurohypophysis.

Topics: Animals; Autoradiography; Dehydration; Hypothalamo-Hypophyseal System; Immunohistochemistry; Iodine Radioisotopes; Male; Nerve Endings; Nerve Fibers; Neuropeptide Y; Peptide YY; Peptides; Rats; Rats, Inbred Strains; Receptors, Neuropeptide Y; Receptors, Neurotransmitter; Sodium Chloride; Water-Electrolyte Balance