scholarly journals Testosterone (T)-Induced Changes in Arcuate Nucleus Cocaine-Amphetamine-Regulated Transcript and NPY mRNA Are Attenuated in Old Compared to Young Male Brown Norway Rats: Contribution of T to Age-Related Changes in Cocaine-Amphetamine-Regulated Transcript and NPY Gene Expression

Endocrinology ◽  
2002 ◽  
Vol 143 (3) ◽  
pp. 954-963 ◽  
Author(s):  
Elliott H. Sohn ◽  
Tami Wolden-Hanson ◽  
Alvin M. Matsumoto
2004 ◽  
Vol 287 (1) ◽  
pp. R138-R146 ◽  
Author(s):  
Tami Wolden-Hanson ◽  
Brett T. Marck ◽  
Alvin M. Matsumoto

Aging mammals lose the ability to maintain energy balance, exhibiting decreased appetite (anorexia) and impaired ability to maintain body weight. To determine the contribution of hypothalamic neuropeptides, two experiments were performed in male Brown Norway rats. To assess the hypothalamic neuropeptide response to food deprivation, young (Y; 4 mo old), middle-aged (M; 13 mo), and old (O; 25 mo) rats were either ad libitum fed or fasted for 72 h ( n = 10/group) and killed. Hypothalamic levels of agouti-related peptide (AgRP), proopiomelanocortin (POMC), and cocaine-amphetamine-regulated transcript (CART) mRNA were assessed by in situ hybridization. With aging, arcuate AgRP gene expression decreased and CART mRNA increased, but POMC mRNA did not change. Fasting-induced changes in gene expression of all neuropeptides studied were attenuated with aging. To test the food intake response to appetite-stimulating neuropeptides, Y, M, O, and very old (VO; 33 mo) rats ( n = 4–8/group) received one intracerebroventricular injection of each of three treatments: 0.1 nmol AgRP, 2.34 nmol NPY, and saline control. AgRP increased food intake of all groups by 10–20%, compared with saline, and this effect persisted up to 7 days after injection. VO animals were more sensitive to the effects of AgRP than younger animals. In contrast, NPY increased food intake more in Y than in older animals and its effects did not last >24 h. We conclude that the mechanisms by which arcuate nucleus neurons influence appetite are differentially affected by age and speculate that the melanocortin system may be a useful target for treatment of the anorexia of aging.


Neuroreport ◽  
2009 ◽  
Vol 20 (17) ◽  
pp. 1534-1537 ◽  
Author(s):  
Emily R. Rosario ◽  
Lilly Chang ◽  
Tina L. Beckett ◽  
Jenna C. Carroll ◽  
M. Paul Murphy ◽  
...  

2014 ◽  
Vol 135 ◽  
pp. 180-188 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry Beltz ◽  
Alan Kim Johnson

Metabolism ◽  
1995 ◽  
Vol 44 (3) ◽  
pp. 320-324 ◽  
Author(s):  
Stephen J. Giddings ◽  
Lynn R. Carnaghi ◽  
Arshag D. Mooradian

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ian R Lanza ◽  
Daniel K Short ◽  
Kevin R Short ◽  
Yan W Asmann ◽  
Sreekumar Raghavakaimal ◽  
...  

2020 ◽  
Author(s):  
Ashani Weeraratna ◽  
Mitchell Fane ◽  
Stephen Douglass ◽  
Gretchen Alicea ◽  
Marie Webster ◽  
...  

Abstract Dormant tumor cells escape the primary site, do not grow out into macroscopic tumors in the distal site, but maintain enough plasticity to reactivate and form overt metastatic lesions, sometimes taking several decades. Despite its importance in metastasis and residual disease, few studies have been able to successfully model or characterize dormancy within melanoma. Here, we show that age-related changes in the lung microenvironment facilitate a permissive niche for efficient outgrowth of disseminated dormant tumor cells, in contrast to the aged skin, where age-related changes suppress melanoma growth but drive dissemination. A model of melanoma progression that addresses these microenvironmental complexities is the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1–3. Dermal fibroblasts are key orchestrators of promoting phenotype switching in melanoma via changes in the secretion of soluble factors during aging4–8. Specifically, we have identified Wnt5A as a master regulator of activating metastatic dormancy, which enables efficient seeding and survival of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble Wnt antagonist sFRP1, which inhibits Wnt5A, enabling efficient metastatic outgrowth. Further, we have identified the tyrosine kinase receptors AXL and MER as promoting a dormancy-to-reactivation axis respectively. Overall, we find that age-induced changes in distal metastatic microenvironments promotes efficient reactivation of dormant melanoma cells in the lung.


1999 ◽  
Vol 87 (4) ◽  
pp. 1373-1380 ◽  
Author(s):  
Ferenc Peták ◽  
Janet L. Wale ◽  
Peter D. Sly

We investigated the effects of a selective β2-agonist, salbutamol, and of phosphodiesterase type 4 inhibition with 4-(3-butoxy-4-methoxy benzyl)-2-imidazolidinone (Ro-20-1724) on the airway and parenchymal mechanics during steady-state constriction induced by MCh administered as an aerosol or intravenously (iv). The wave-tube technique was used to measure the lung input impedance (Zl) between 0.5 and 20 Hz in 31 anesthetized, paralyzed, open-chest adult Brown Norway rats. To separate the airway and parenchymal responses, a model containing an airway resistance (Raw) and inertance (Iaw), and a parenchymal damping (G) and elastance (H), was fitted to Zl spectra under control conditions, during steady-state constriction, and after either salbutamol or Ro-20-1724 delivery. In the Brown Norway rat, the response to iv MCh infusion was seen in Raw and G, whereas continuous aerosolized MCh challenge produced increases in G and H only. Both salbutamol, administered either as an aerosol or iv, and Ro-20-1724 significantly reversed the increases in Raw and G when MCh was administered iv. During the MCh aerosol challenge, Ro-20-1724 significantly reversed the increases in G and H, whereas salbutamol had no effect. These results suggest that, after MCh-induced changes in lung function, salbutamol increases the airway caliber. Ro-20-1724 is effective in reversing the airway narrowings, and it may also decrease the parenchymal constriction.


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