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41.
D.V. Coscina J.W. Chambers I. Park S. Hogan J. Himms-Hagen 《Brain research bulletin》1985,14(6):585-593
Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, after biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4-5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4 degrees C for 21 hr or remained at 28 degrees C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28 degrees C. Exposure to 4 degrees C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable "cafeteria" diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4-5 weeks later, KC rats had gained 3-4 times more weight than controls and were obese. Interscapular BAT weighed 200-300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
42.
K. Andersson K. Fuxe P. Eneroth L. F. Agnati A. Härfstrand 《Naunyn-Schmiedeberg's archives of pharmacology》1987,335(5):521-528
Summary The effects of acute continuous exposure to the smoke from 1–4 cigarettes have been studied in the male rat in terms of hypothalamic catecholamine levels and utilization as well as the secretion of anterior pituitary hormones. Catecholamine levels in discrete hypothalamic catecholamine nerve terminal systems were studied by quantitative histofluorimetry. Catecholamine utilization was studied by means of the tyrosine hydroxylase inhibition method using -methyl-(±)-p-tyrosine methyl ester. The serum hormone levels of adenohypophyseal hormones and of corticosterone were measured by the use of radioimmunoassay procedures. The results show that acute continuous exposure to unfiltered but not to filtered (Cambridge glass fibre filters) cigarette smoke leads to small but dose-dependent reductions of amine levels in most of the hypothalamic noradrenaline and dopamine nerve terminal system. These effects were associated with an enhancement of regional hypothalamic noradrenaline utilization but not of dopamine utilization in the median eminence. Furthermore, a reduction of TSH and prolactin serum levels was noted as well as increases in ACTH secretion. These results are partly different from those previously obtained with rats acutely exposed to intermittent unfiltered cigarrete smoke. This difference is suggested to be due to a temporary blockade of catecholamine release following acute continuous exposure to cigarette smoke.This work has been supported by a grant (1223) from the Council for Tobacco Research, New York, USA and by a grant from the Svenska Tobaks monopolet
Send offprint requests to K. Andersson at the above address 相似文献
43.
A classic feature of animals with lateral hypothalamic (LH) lesions is their regulation of body weight at sub-normal levels. The present studies were done to determine whether this is associated with enhanced thermogenic activity of their brown adipose tissue (BAT). Three groups of young chow-fed male Holtzman rats were formed: (1) animals receiving bilateral radiofrequency heat lesions of the dorsal LH and then permitted free access to chow (LH rats); (2) non-lesioned animals that were pair-fed (PF) to the lesioned rats during a 2 week post-operative recovery period (Phase 1); (3) non-lesioned, ad lib fed (NORM) controls. After Phase 1, each group was divided and permitted free access to chow alone or an additional selection of palatable, novel food items (a "cafeteria" diet) for 2-3 weeks (Phase 2) to stimulate diet-induced thermogenesis in BAT. Finally, half of each sub-group was exposed to 4 degrees C for 15 hr to stimulate nonshivering thermogenesis in BAT. During Phase 1 LHs and PFs ate 50% less than NORMs. This resulted in a weight deficit of 16% for LHs and 12% for PFs. After the additional period of feeding palatable foods (Phase 2) LHs collectively weighed 14% less than NORMs whereas previously PFs had a weight deficit of only 4%. They gained less weight than NORMs or PFs despite a similar energy intake. LHs had small deposits of gonadal white adipose tissue [both total amount and expressed per metabolic body mass (kg 0.75)]. The weight of interscapular BAT was less in the LHs but its concentration of protein (mg/g) was higher.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
44.
Pharmacologic blockade of GABA binding sites in the hypothalamus elicits a pattern of physiological and behavioral arousal. The latter outcome implicates a perturbation in the neural functioning of higher brain centers. The effect that hypothalamic GABAA receptor modulation has on the function of cerebral cortical neural substrates linked with responses to stressors was assessed using microinfusion of bicuculline methiodide (BMI) into the medial hypothalamus of freely moving, handling habituated rats. BMI led to rapid increases in frontal cortical dopamine (DA) utilization (calculated from the sum of the levels of the DA metabolites, homovanilic and dihydroxyphenylacetic acids, divided by DA levels) resembling that identified following restraint-induced stress. Also, cortical GABAA receptor function [using chloride (Cl–) enhancement of3H-flunitrazepam (Flu) binding as an index] was disrupted; i.e. there was a loss of typical Cl– enhancement of3H-Flu binding in animals after BMI infusions. However, placing animals in restraint after BMI infusion reversed the effects of BMI, with both DA utilization and Cl– facilitated3H-Flu binding similar to control basal values. Muscimol infusions in separately prepared animals did not alter either frontal cortical DA utilization or GABAA receptor function. The present results implicate GABA in the hypothalamus as gating activity of cortical systems involved in sensation of and/or responses to stressors. These findings may have important implications for effects of autonomic arousal on neural substrates involved in mediating stress responses. 相似文献
45.
Increased NPY activity in the PVN contributes to food-restriction induced reductions in blood pressure in aortic coarctation hypertensive rats 总被引:2,自引:0,他引:2
We hypothesized that hypothalamic NPYergic mechanisms mediate the blood pressure lowering effect of caloric restriction in hypertensive rats. Aortic coarctation-induced (AC) hypertensive rats (n=25) were assigned to either an ad libitum fed control group (AL) or food restricted group (FR; 60% of AL consumption) for 3 weeks. Rats were instrumented chronically with vascular catheters and bilateral guide cannulae directed at the paraventricular hypothalamic nuclei (PVN). Blood pressure (BP) and heart rate (HR) responses to bilateral PVN microinjection of saline (200 nl) or the putative NPY receptor antagonists [D-Trp32]NPY(1-36) (3.3 micrograms/200 nl) and [D-Tyr27,36 Thr32]NPY(27-36) (D-NPY(27-36); 3.3 micrograms/200 nl) were determined. The FR rats were then refed and cardiovascular responses to PVN injections of NPY receptor antagonists were again determined. FR rats had significantly reduced resting BP (159+/-4 vs. 129+/-4 mmHg) and HR (360+/-11 vs. 326+/-9 bpm) compared to AL controls. Refeeding restored BP and HR of FR rats to levels similar to AL (BP=153+/-4 mmHg, HR=359+/-11 bpm). PVN administration of [D-Trp32]NPY produced foraging behavior and concurrent increases in BP and HR in FR, AL and Re-fed rats. The behavioral activation suggests that [D-Trp32]NPY(1-36) produced activation of NPY receptors. In contrast, D-NPY (27-36) did not produce any behavioral response or affect BP or HR in AL or Re-fed rats. In FR rats, D-NPY (27-36) produced significant increases in BP (peak=15+/-3 mmHg) which partially reversed the effect of FR on BP. Thus, in FR rats with reduced BP, PVN administration of an NPY receptor antagonist increases BP. NPY blockade in the PVN accounted for about 50% of the BP effect of food restriction, thus other mechanisms are likely to be involved. These findings are consistent with the hypothesis that NPYergic mechanisms may contribute to the reduction of BP produced by food restriction. 相似文献
46.
Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus 总被引:11,自引:0,他引:11
Mechanisms mediating genetic susceptibility to diet-induced obesity have not been completely elucidated. Elevated hypothalamic neuropeptide Y (NPY) and decreased hypothalamic proopiomelanocortin (POMC) are thought to promote the development and maintenance of obesity. To assess the potential role of hypothalamic neuropeptide gene expression in diet-induced obesity, the present study examined effects of a high-fat diet on hypothalamic NPY and POMC mRNA in three strains of mice that differ in susceptibility to develop diet-induced obesity. C57BL/6J, CBA, and A/J mice were fed either normal rodent chow or a high-fat diet for 14 weeks after which hypothalamic gene expression was measured. On the high-fat diet, C57BL/6J mice gained the most weight, whereas A/J mice gained the least weight. On the high-fat diet, NPY mRNA significantly decreased as body weight increased in CBA and A/J mice, but not in C57BL/6J mice. In addition, POMC mRNA significantly increased as body weight increased in A/J mice, but not in CBA and C57BL/6J mice. Since decreased NPY mRNA and increased POMC mRNA would presumably attenuate weight gain, these results suggest that a high-fat diet produces compensatory changes in hypothalamic gene expression in mice resistant to diet-induced obesity but not in mice susceptible to diet-induced obesity. 相似文献
47.
Rationale: Although physically aversive stimuli induce functional changes in central noradrenergic neurones, little is known about the
noradrenergic response to environmentally aversive stimuli. Objectives: The first aim was to characterise environmental features that are perceived as stressful by rats. The second was to investigate
whether changes in the concentration of extracellular noradrenaline are induced by these environmental features. Methods: A light/dark shuttle-box was used to test rats’ behavioural response to a range of stimuli (novelty, bright light, and the
presence of an unfamiliar rat), either before or after microdialysis probe implantation. Changes in the concentration of extracellular
noradrenaline in the frontal cortex and hypothalamus in vivo were then evaluated on exposure to these same test conditions. Results: Naive rats spent less time in a brightly-lit test arena than a dark one. However, the behavioural response to the light arena
was attenuated by the presence of an unfamiliar rat. Probe implantation intensified the response to the light arena but did
not affect behaviour in the dark arena. In the microdialysis studies, there was no change in the concentration of extracellular
noradrenaline on transfer of rats to the dark arena but there was an increase in both the frontal cortex (+45%) and hypothalamus
(+75%) on exposure to the light arena. A similar increase was induced in both brain regions when the light arena contained
an unfamiliar rat. Conclusions: Implantation of a microdialysis probe modifies the behavioural responses to certain environmental stimuli. Regardless of
this, the extent to which rats perceive a novel environment as aversive is not the only determinant of the noradrenergic response
to such stimuli. However, differences in stimulus controllability in the microdialysis and the behavioural experiments could
influence the apparent intensity of the stress.
Received: 29 October 1998 / Final version: 19 March 1999 相似文献
48.
Edda Adler-Graschinsky S. Z. Langer 《Naunyn-Schmiedeberg's archives of pharmacology》1978,303(3):243-249
Summary In the isolated nerve-muscle preparation of the cat nictitating membrane exposure to 0.04 M of the scorpion venom tityustoxin (TsTX) increased significantly the overflow of 3H-noradrenaline and the responses elicited by postganglionic nerve stimulation (1200 pulses, 0.5 ms duration, supramaximal voltage). Concentration effect curves to exogenous (-)-noradrenaline were not affected in the presence of this concentration of TsTX.The enhanced release of 3H-noradrenaline obtained during nerve stimulation as well as the increase of the postsynaptic responses observed during exposure to TsTX were more pronounced at 4 Hz than at 20 Hz. The increase in the overflow of noradrenaline observed with the toxin was selective for nerve stimulation since the release evoked by tyramine was not affected by TsTX.TsTX did not increase further the enhancement of 3H-noradrenaline release obtained in the presence of 18 mM tetraethylammonium (TEA). On the other hand, both TsTX and TEA were able to increase further the overflow of 3H-noradrenaline after block of the presynaptic alpha-adrenoceptors with phenoxybenzamine 0.29 or 2.9 M.In slices of rat cerebral cortex, TsTX 0.04 M increased 3H-noradrenaline release induced by 10 mM and by 20 mM KCl. The increased release evoked by the toxin was more pronounced for the lower concentration of K+.An increased release of 3H-noradrenaline in the presence of the toxin was also observed in rat hypothalamic slices stimulated with 20 mM K+. The K+ stimulated induced release of 3H-noradrenaline was also increased by 1.8 mM TEA. As shown for the peripheral nervous, system the simultaneous addition of TEA and TsTX did not result in additive effects when compared with the effects of the two agents added separately. Tityustoxin did not modify the metabolic pattern of the neurotransmitter released by K+ from rat hypothalamic slices.It is concluded that TsTX increases the stimulation-induced release of 3H-noradrenaline from both peripheral and central noradrenergic nerve terminals. Tityustoxin appears to act on the nerve terminal by a mechanism similar to that of TEA, an agent known to enhance the amount of noradrenaline released by nerve stimulation by increasing the duration of the action potentials. 相似文献
49.
Neonatal mice 1 and 5 days of age and older mice 25 days of age were injected with an increasing dose of monosodium glutamate (MSG) for a ten-day period and observed for at least 150 days. Both male and female animals in the 1- and 5-day age group treated with MSG showed large increases in weight over controls along with a shortened body length. The MSG group also showed decreases in locomotor and explatory behavior. The 25-day animals took much longer to show effects or failed to show any effects, indicating that the MSG-induced changes studied are age dependent. Possible methodological considerations accounting for conflicting reports in the MSG literature are discussed in light of the present findings. 相似文献
50.
针刺对糖尿病大鼠下丘脑神经肽Y及其mRNA表达的影响 总被引:3,自引:0,他引:3
目的:观测针刺对STZ所导致的糖尿病大鼠下丘脑NPY及其mRNA表达的影响。方法:Wistar大鼠4 3只,1 3只为正常对照,另30只行链脲左菌素腹腔注射造模,造模成功的大鼠随机分为模型组和针刺治疗组(针刺“胰俞”“足三里”“关元”) ,针刺治疗2个疗程后取脑,运用免疫组化法和原位杂交法分别检测下丘脑NPY蛋白及其mRNA的表达。结果:STZ糖尿病大鼠下丘脑室旁核、弓状核NPY阳性纤维较正常组大鼠明显增多,下丘脑外侧区NPYmRNA表达较正常明显增多(P <0 .0 5 ) ,针刺治疗后糖尿病大鼠下丘脑室旁核、弓状核NPY阳性纤维及下丘脑外侧区NPYmRNA表达明显减少(P <0 .0 5 )。结论:针刺可以降低STZ糖尿病大鼠下丘脑增多的NPY的合成及其含量,这可能是针刺改善糖尿病能量代谢的中枢机制之一。 相似文献