Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.
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PMID:Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats. 131 58

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.
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PMID:Blunted hypothalamic neuropeptide gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats. 1500 33

Both growth hormone (GH)/insulin growth factor (IGF)-1 axis and energy balance have been implicated in longevity independently. The aim of the present study was to characterize the effect of a 72-h fasting period at 3 months of age in four different rat strains: (i) Wistar and (ii) Fischer 344 rats, which develop obesity with age, and (iii) Brown Norway and (iv) Lou C rats, which do not. Wistar rats ate more, were significantly bigger, and presented with higher plasma leptin and lower ghrelin levels and hypothalamic growth hormone-releasing hormone (GHRH) content than rats from the three other strains. Plasma insulin and IGF-1 levels were lower in Brown Norway and Lou C rats, and somatostatin content was lower in Brown Norway rats only. Glycaemia was lower in Lou C rats that displayed a lower relative food intake compared to Fischer and Wistar rats. Brown Norway rats showed a greater caloric efficiency than the three other strains. Concerning major hypothalamic neuropeptides implicated in feeding, similar amounts were detected in the four strains for neuropeptide Y, agouti-related peptide, galanin, melanin-concentrating hormone, alpha-melanocortin-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone. Orexin A appeared to be slightly elevated in Fischer rats and cocaine amphetamine-regulated transcript (CART)(55-102) diminished in Brown Norway. At the mRNA level, orexin A, GHSR1, alpha-MSH and CART expression were higher in Wistar and Lou C rats. Principal component analysis confirmed the presence of two main factors in the ad libitum rat population; the first being associated with growth-related parameters and the second being associated with food intake regulation. Hypothalamic GHRH and somatostatin content were positively correlated with feeding-related neuropeptides such as alpha-MSH for GHRH, and orexin A and CART for both peptides. Plasma ghrelin levels were negatively correlated with leptin and IGF-1 levels. Finally, a 72-h fasting period affected minimally body weight, plasma IGF-1 and leptin levels in Lou C rats compared to the three other strains, and plasma insulin levels were less affected in Brown Norway rats. In conclusion, Wistar shorter life span is consistent with its already fatter phenotype at 3 months of age. In terms of IGF-1, glycaemia and leptin responses to fasting, the Lou strain, which presents with a low food intake/body weight and caloric efficiency, is the least affected. The link between food intake regulation, GH axis and ageing is further demonstrated by principal component analysis, where GHRH and somatostatin were found to be strongly associated with energy homeostasis parameters.
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PMID:Plasma and hypothalamic peptide-hormone levels regulating somatotroph function and energy balance in fed and fasted states: a comparative study in four strains of rats. 1566 53

We used three inbred rat strains known for significant differences in the activity and reactivity of their hypothalamic-pituitary-adrenal (HPA) axis to stress [Fischer 344 (F344), Brown Norway (BN) and Lewis (Lew) rats] to search for a strain difference in the paradoxical increase in running activity induced by food restriction and to explore the role of the HPA axis in this behaviour. Rats were randomly assigned to either an ad lib sedentary group (AL), a control wheel activity group (ACT), a food restriction-induced hyperactivity group (FR-ACT) group (1.5 h/day ad lib food, 22.5 h/day ad lib wheel access) or a pair-fed group (FR). The BN and Lew rats reached the 25% body weight-loss criterion of FR-ACT (strain effect: F(2,132) = 45.58, P < 10-6) faster than the F344 strain due to higher food restriction-induced running activity (strain effect: F(2,65) = 17.43, P = 0.00001). FR and FR-ACT decreased thymus weight (marker of integrated HPA axis activation) in all strains. In Lew and BN strains, FR-ACT induced a further decrement on thymus weight compared to their FR group. Prefeeding corticosterone levels (15.00 h) increased during the study in BN and Lew FR-ACT rats, but not in F344. Total wheel turns were correlated to both final adipose weight (r = -0.49, P = 0.002) and thymus weight decrement (r = 0.59, P = 0.0001), emphasizing the relationship between fat mass and HPA axis activation in excessive running activity. Increased running in conditions of food restriction and HPA axis activation may be linked at the level of the central nervous system. However, the involvement of corticotrophin-releasing hormone, agouti-related peptide or cocaine- and amphetamine-regulated transcript in behavioural disturbances of FR-ACT rats was excluded (in situ hybridization). We propose that corticosterone may be the link between initial low levels of fat mass and/or rate of fat mass loss (peripheral energy stores) and increased wheel activity, favouring fueling through lipolysis and proteolysis and reinforcing the self starvation via reward mechanisms, thus establishing a deleterious vicious cycle.
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PMID:Genetic differences in hypothalamic-pituitary-adrenal axis activity and food restriction-induced hyperactivity in three inbred strains of rats. 1621 3

Enhancing survival to hemorrhage of both civilian and military patients is a major emphasis for trauma research. Previous observations in humans and outbred rats show differential survival to similar levels of hemorrhage. In an initial attempt to determine potential genetic components of such differential outcomes, survival time after a controlled hemorrhage was measured in 15 inbred strains of rats. Anesthetized rats were catheterized, and approximately 24 h later, 55% of the calculated blood volume was removed during a 26-min period from conscious unrestrained animals. Rats were observed for a maximum of 6 h. Survival time was 7.7-fold longer in the longest-lived strain (Brown Norway/Medical College of Wisconsin; 306 +/- 36 min; mean +/- SEM) than in the shortest-lived strain (DA; 40 +/- 5 min; P < or = 0.01). Mean survival times for the remaining inbred strains ranged from 273 +/- 44 to 49 +/- 4 min (Dahl-Salt Sensitive > Brown Norway > Munich Wistar Fromter> Dahl-Salt Resistant > Copenhagen > Noble > Spontaneous-hypertensive > Lewis > BDIX > Fawn Hooded Hypertensive > FISCHER 344 > Black agouti > PVG). The variance in the hazard of death attributable to different strains was estimated to be 1.22 log-hazard units, corresponding to a heritability of approximately 48%. Graded and divergent survival times to hemorrhage in inbred rat strains are remarkable and suggest multiple genetic components for this characteristic. However, this interpretation of differential responses to hemorrhage may be confounded by potential strain-associated differences related to the surgical preparation. Identification of inbred strains divergent in survival time to hemorrhage provides the opportunity for future use of these strains to identify genes associated with this complex response.
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PMID:Is survival time after hemorrhage a heritable, quantitative trait?: an initial assessment. 1799 86