Chronic Administration of Glucocorticoids Directly Upregulates Prepro-Neuropeptide Y and Y1-Receptor mRNA Levels in the Arcuate Nucleus of the Rat

In mammals, neuropeptide Y (NPY) is a potent orexigenic factor. In the present study, third brain ventricle (intracerebroventricular) injection of goldfish NPY (gNPY) caused a dose-dependent increase in food intake in goldfish, and intracerebroventricular administration of NPY Y1-receptor antagonist BIBP-3226 decreased food intake; the actions of gNPY were blocked by simultaneous injection of BIBP-3226. Goldfish maintained on a daily scheduled feeding regimen display an increase in NPY mRNA levels in the telencephalon-preoptic area and hypothalamus shortly before feeding; however, a decrease occured in optic tectum-thalamus. In both fed and unfed fish, brain NPY mRNA levels decreased after scheduled feeding. Restriction in daily food ration intake for 1 wk or food deprivation for 72 h resulted in increased brain NPY mRNA levels. Results from these studies demonstrate that NPY is a physiological brain signal involved in feeding behavior in goldfish, mediating its effects, at least in part, through Y1-like receptors in the brain.

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Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation

Journal of Neuroscience ◽

10.1523/jneurosci.14-11-06423.1994 ◽

1994 ◽

Vol 14 (11) ◽

pp. 6423-6434 ◽

Cited By ~ 111

Author(s):

RR Ji ◽

X Zhang ◽

Z Wiesenfeld-Hallin ◽

T Hokfelt

Keyword(s):

Spinal Cord ◽

Neuropeptide Y ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Peripheral Tissue ◽

Rat Spinal Cord ◽

Tissue Inflammation ◽

Y1 Receptor ◽

Receptor Mrna

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Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event

Journal of Molecular Endocrinology ◽

10.1677/jme.1.01819 ◽

2005 ◽

Vol 35 (1) ◽

pp. 159-164 ◽

Cited By ~ 45

Author(s):

Martien J H Kas ◽

Adrie W Bruijnzeel ◽

Jurgen R Haanstra ◽

Victor M Wiegant ◽

Roger A H Adan

Keyword(s):

Neuropeptide Y ◽

Hpa Axis ◽

Arcuate Nucleus ◽

Eating Behaviour ◽

Melanocortin Receptor ◽

Stressful Event ◽

Mrna Levels ◽

Related Protein ◽

Increased Sensitivity ◽

Agouti Related Protein

Stress affects eating behaviour in rodents and humans, suggesting that the regulation of energy balance and the stress response are coupled physiological processes. Neuropeptide Y (NPY) and agouti-related protein (AgRP) are potent food-stimulating neuropeptides that are highly co-localised in arcuate nucleus neurons of the hypothalamus. Recent studies have shown that NPY and AgRP mRNA levels in these neurons respond similarly to fasting and leptin, indicating functional redundancy of the neuropeptide systems in these orexigenic neurons. However, we have found that NPY and AgRP mRNA expression in arcuate nucleus neurons are dissociated immediately following a stressful event. Two hours following a brief session of inescapable foot shocks, AgRP mRNA levels are down-regulated (P < 0.0001). In contrast, NPY mRNA levels are up-regulated (P < 0.0001). To provide physiological relevance for this acute down-regulation of AgRP, an inverse agonist of melanocortin receptors, we have shown that acute intracerebroventricular injection of a melanocortin receptor agonist, α-melanocyte-stimulating hormone (α-MSH), caused a significantly stronger activation of the hypothalamus–pituitary–adrenal-cortical (HPA) axis following a stressful event than in controls. Thus, AgRP and NPY mRNA levels in similar arcuate nucleus neurons are differentially regulated following a stressful event. This may contribute to increased sensitivity for α-MSH to activate the HPA axis following a repeated stressful experience.

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Altered Expression of Agouti-Related Protein and Its Colocalization with Neuropeptide Y in the Arcuate Nucleus of the Hypothalamus during Lactation*

Endocrinology ◽

10.1210/endo.140.6.6829 ◽

1999 ◽

Vol 140 (6) ◽

pp. 2645-2650 ◽

Cited By ~ 59

Author(s):

Peilin Chen ◽

Chien Li ◽

Carrie Haskell-Luevano ◽

Roger D. Cone ◽

M. Susan Smith

Keyword(s):

In Situ Hybridization ◽

Food Intake ◽

Neuropeptide Y ◽

Arcuate Nucleus ◽

Mrna Levels ◽

Related Protein ◽

Altered Expression ◽

Caudal Portion ◽

Agouti Related Protein

Abstract During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important role in the regulation of food intake. In the first experiment, animals were studied during diestrus of the estrous cycle, a stage of the cycle when estrogen levels are basal and similar to lactation, or during days 12–13 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue sections were used to measure AGRP messenger RNA (mRNA) levels by in situ hybridization. AGRP mRNA signal was found mostly in the ventromedial portion of the ARH, which has been shown to contain a high density of NPY neurons. A significant increase in AGRP mRNA content was observed in the mid- to caudal portion of the ARH of lactating animals compared with diestrous females. No difference was found in the rostral portion of the ARH. In the second experiment, double-label in situ hybridization for AGRP and NPY was performed in lactating animals to determine the extent of colocalization of the two peptides in the ARH, using 35S-labeled and digoxigenin-labeled antisense complementary RNA probes. It was found that almost all of the NPY-positive neurons throughout the ARH also expressed AGRP mRNA signal. Furthermore, AGRP expression was confined almost exclusively to NPY-positive neurons. Thus, the present study showed that during lactation, AGRP gene expression was significantly elevated in a subset of the AGRP neurons in the ARH. The high degree of colocalization of AGRP and NPY, coupled with previous reports from our laboratory demonstrating increased NPY expression in the ARH in response to suckling, suggests that AGRP and NPY are coordinately regulated and may be involved in the increase in food intake during lactation.

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Basomedial Hypothalamic Injections of Neuropeptide Y Conjugated to Saporin Selectively Disrupt Hypothalamic Controls of Food Intake

Endocrinology ◽

10.1210/en.2004-1166 ◽

2005 ◽

Vol 146 (3) ◽

pp. 1179-1191 ◽

Cited By ~ 49

Author(s):

Kishor Bugarith ◽

Thu T. Dinh ◽

Ai-Jun Li ◽

Robert C. Speth ◽

Sue Ritter

Keyword(s):

Neuropeptide Y ◽

Arcuate Nucleus ◽

Retrograde Transport ◽

Related Protein ◽

Y1 Receptor ◽

Npy Receptor ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Glucoprivic Feeding ◽

Agouti Gene

Neuropeptide Y (NPY) conjugated to saporin (NPY-SAP), a ribosomal inactivating toxin, is a newly developed compound designed to selectively target and lesion NPY receptor-expressing cells. We injected NPY-SAP into the basomedial hypothalamus (BMH), just dorsal to the arcuate nucleus (ARC), to investigate its neurotoxicity and to determine whether ARC NPY neurons are required for glucoprivic feeding. We found that NPY-SAP profoundly reduced NPY Y1 receptor and αMSH immunoreactivity, as well as NPY, Agouti gene-related protein (AGRP), and cocaine and amphetamine-related transcript mRNA expression in the BMH. NPY-SAP lesions were localized to the injection site with no evidence of retrograde transport by hindbrain NPY neurons with BMH terminals. These lesions impaired responses to intracerebroventricular (icv) leptin (5 μg/5 μl·d) and ghrelin (2 μg/5 μl), which are thought to alter feeding primarily by actions on ARC NPY/AGRP and proopiomelanocortin/cocaine and amphetamine-related transcript neurons. However, the hypothesis that NPY/AGRP neurons are required downstream mediators of glucoprivic feeding was not supported. Although NPY/AGRP neurons were destroyed by NPY-SAP, the lesion did not impair either the feeding or the hyperglycemic response to 2-deoxy-d-glucose-induced blockade of glycolysis use. Similarly, responses to glucagon-like peptide-1 (GLP-1, 5 μg/3 μl icv), NPY (5 μg/3 μl icv), cholecystokinin octapeptide (4 μg/kg ip), and β-mercaptoacetate (68 mg/kg ip) were not altered by the NPY-SAP lesion. Thus, NPY-SAP destroyed NPY receptor-expressing neurons in the ARC and selectively disrupted controls of feeding dependent on those neurons but did not disrupt peptidergic or metabolic controls dependent upon circuitry outside the BMH.

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Effects of gold thioglucose on neuropeptide Y messenger RNA levels in the mouse hypothalamus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.6.r1208 ◽

1996 ◽

Vol 270 (6) ◽

pp. R1208-R1214 ◽

Cited By ~ 1

Author(s):

J. L. Marks ◽

K. Waite ◽

D. Cameron-Smith ◽

S. C. Blair ◽

G. J. Cooney

Keyword(s):

Neuropeptide Y ◽

Messenger Rna ◽

Arcuate Nucleus ◽

Early Stage ◽

Ventromedial Hypothalamus ◽

Mrna Levels ◽

Gold Thioglucose ◽

Deep Layers ◽

Overnight Fasting ◽

Late Stages

Elevated hypothalamic neuropeptide Y (NPY) expression is found in several rodent genetic models of obesity, but any association in nongenetic models of obesity is unclear. Consequently, we have measured NPY mRNA levels in the ventromedial hypothalamus of a well-characterized model of obesity, the gold thioglucose (GTG)-injected mouse. Fourteen days after injection (early stage), animals were hyperphagic but not obese, hyperglycemic, or overtly hyperinsulinemic. Ten weeks after treatment (late stage), animals were obese, markedly hyperinsulinemic, and hyperglycemic. In both the early and late stages, NPY mRNA levels were reduced in the arcuate nucleus of GTG-injected animals. Although overnight fasting doubled NPY mRNA levels in control animals, there was no change at either stage in GTG-injected animals. NPY mRNA levels in the deep layers of the cerebral cortex and in the dentate gyrus were not affected by GTG treatment or overnight fasting. We conclude that GTG treatment reduces the expression of NPY mRNA in the arcuate nucleus and that, therefore, increased hypothalamic NPY expression is unlikely to be an important factor causing the obesity and other metabolic changes found in this model.

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