Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary-adrenocortical axis in the rat

Wahlestedt, Claes; Skagerberg, Gunnar; Ekman, Rolf; Heilig, Markus; Sundler, F.; Håkanson, R.

doi:10.1016/0006-8993(87)90176-4

Cited by 283 publications

(118 citation statements)

References 20 publications

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“…Within the hypothalamus, NPY expressing neurons located in the arcuate nucleus project to the paraventricular nucleus, where NPY interacts with CRHergic neurons and thus modulates the reactivity and sensitivity of the HPA axis (Wahlestedt et al, 1987;Haas and George, 1987). In the present study, there was no strain difference in either hypothalamic CRH-LI or serum corticosterone.…”

Section: Discussioncontrasting

confidence: 39%

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Husum

Kammen

Termeer

et al. 2003

Neuropsychopharmacol

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Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY-and galanin-like immunoreactivities (LI) while NPY-and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.

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Section: Discussioncontrasting

confidence: 39%

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Husum

Kammen

Termeer

et al. 2003

Neuropsychopharmacol

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“…This possibility awaits further investigation. There is also evidence that CRH synthesis and release in the median eminence may be stimulated by NPY (52)(53)(54). The interaction of NPY and CRH in the paraventricular nucleus provide opposing mechanisms in regulating food intake, because the CRH antagonist, ␣-helical CRH9 -41, enhances NPY-induced food intake (55,56).…”

Section: Discussionmentioning

confidence: 99%

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

et al. 2002

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Effects of a high-fat diet and strain on hypothalamic gene expression in rats. Obes Res. 2002;10:1188 -1196. Objective: This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake. Research Methods and Procedures: Three-month-old Osborne-Mendel (OM) and S5B/Pl rats were fed either a high-fat or a low-fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin-releasing hormone, NPY Y-1 receptor and Y-5 receptor, and serotonin 2c (5-HT2c) receptors were measured using Northern blotting or ribonuclease protection assays. Results: OM rats showed an increased expression of NPY and corticotrophin-releasing hormone compared with S5B/Pl rats. The expression of NPY-Y1 and -Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT-2c receptor mRNA was significantly reduced in both strains of rats eating a high-fat diet when compared with the animals eating the low-fat diet. Discussion: These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT-2c receptor gene may be modulated by dietary fat.

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“…Through projections to the pituitary, this peptide controls the release of adrenocorticotropin releasing hormone ( ACTH ) into the blood and, in turn, the synthesis and secretion of CORT and ALDO from the adrenal glands (23)(24)(25). The release of CRF and the steroids is known to be modulated by a variety of neurochemical systems in the hypothalamus, including the catecholamines, nNPY and serotonin, and the peptide, (26)(27)(28).…”

Section: Adrenal Steroids and Their Receptorsmentioning

confidence: 99%

“…Does this relationship between a neurochemical and a specific nutrient involve the actions of the adrenal steroid, CORT, which also affects carbohydrate stores? An association between circulating CORT and brain NE or NPY is suggested by the stimulatory effect of these neurochemicals on the release of CORT (26,28). In addition, central microinjection studies and analyses of the behavioral responses elicited by these neurochemicals have shown the feeding-stimulatory action of NE, via a2 receptors in the PVN, to be dependent upon and positively correlated with circulating CORT levels (209) and, also, a similar dependence on CORT of the feeding response elicited by PVN NPY at a Y,-like receptor (191,210).…”

Section: Adrenal Steroid Receptors In the Brainmentioning

confidence: 99%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

194

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary-adrenocortical axis in the rat

Cited by 283 publications

References 20 publications

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Topiramate Normalizes Hippocampal NPY-LI in Flinders Sensitive Line ‘Depressed’ Rats and Upregulates NPY, Galanin, and CRH-LI in the Hypothalamus: Implications for Mood-Stabilizing and Weight Loss-Inducing Effects

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

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