Eckhart Simon

Regional differentiation of sympathetic activity during hypothalamic heating and cooling in anesthetized rabbits.

SummaryIn anesthetized rabbits immobilized with succinyl choline, the discharges of sympathetic efferents supplying cutaneous and visceral regions were simultaneously recorded. The effects of thermal stimulation of the hypothalamic region were tested on the basis of the integrated discharges. During hypothalamic heating cutaneous sympathetic activity decreased, corresponding to increased ear blood flow, while visceral sympathetic activity increased. During hypothalamic cooling there was, on the average, no significant change of regional sympathetic activity. However, in single experimental periods an increase of cutaneous and a decrease of visceral sympathetic activity was found.The observed responses of regional sympathetic activity were compared with findings about regional cutaneous and intestinal blood flow under the same thermal stimulus and further with corresponding former investigations on regional blood flow and regional sympathetic activity during spinal thermal stimulation. It is suggested by this comparison that regional differentiation of sympathetic activity represents a specific thermoregulatory response of the vasomotor system mediated by the hypothalamic thermoregulatory center.

Mammalian and avian antidiuretic hormone: Studies related to possible species variation in osmoregulatory systems

Summary1.In two representative species of the mammalian and avian classes, the dog and Pekin duck, antidiuretic hormone (ADH) concentrations in the blood were measured by a common radioimmunoassay (RIA) making use of an antiserum raised against the mammalian ADH, arginine vasopressin (AVP) which also cross reacted with the avian ADH, arginine vasotocin (AVT), (Fig. 1). The effects of 24 h dehydration on blood osmolality and ADH concentration and the plasma clearance rates of ADH of conscious dogs and Pekin ducks were compared.2.An AVP plasma level of 2.37±0.20 pg·ml−1 (2.18±0.18 fmol·ml−1) (mean±SE) was found in normally hydrated dogs at 298.1±1.0 mOsm· kg−1 plasma osmolality; 24 h water deprivation increased plasma AVP to 6.64±0.96 pg·ml−1 (6.12±0.88 fmol·ml−1) and osmolality to 314.2±2.3 mOsm·kg−1 (Fig. 2). In ducks, osmolality and AVT concentration increased from 297.6±1.2 mOsm·kg−1 and 5.80±0.41 pg·ml−1 (5.51±0.39 fmol·ml−1) in normally hydrated animals to 318.6±3.2 mOsm·kg−1 and 14.46±1.45 pg·ml−1 (13.75±1.38 fmol·ml−1) after 24 h water deprivation (Fig. 3).3.In both species the correlations between plasma osmolality and ADH concentration were highly significant (2 P<0.001) and indicated similar sensitivities of the ADH system to changes in plasma osmolality: 0.24 pg·ml−1 per mOsm·kg−1 in dogs (Fig. 4) and 0.39 pg·ml−1 per mOsm·kg−1 in Pekin ducks (Fig. 5). This interspecies difference in sensitivity was found to be less than the intraspecies variations (Table 1).

Differential stimulation of c-fos expression in hypothalamic nuclei of the rat brain during short-term heat acclimation and mild dehydration

Activation of central nervous structures involved in the perception and integration of thermo- and osmoregulatory signals was investigated in the Sabra rat. Male rats were either non-treated (C-E), water-deprived for 24 h (C-D), short-term acclimated to 34 degrees C for two days (STHA-E) or subjected to both stimuli (STHA-D). Immunoreactivity for c-Fos protein (Fos-IR) as marker for neuronal activation was quantified in (extra-)hypothalamic structures: organum vasculosum laminae terminalis (OVLT); subfornical organ (SFO); medial (MPA), ventromedial preoptic (VMPO) and lateral hypothalamic (LHA) areas; median preoptic (MnPO), magnocellular supraoptic (SON) and paraventricular (mPVN) nuclei; limbic lateral septal (LS) and thalamic paraventricular (PV) nuclei. Compared to C-E rats, dehydration markedly increased Fos-IR exclusively in neurons of the OVLT, SFO and MnPO known to be involved in osmoreception, in the mPVN and SON, and to a minor extent in the VMPO. The VMPO, MPA, LHA and LS-important (extra-)hypothalamic sites for the perception and integration within the thermoregulatory control circuit-exhibited intense elevation of Fos-IR upon short-term heat acclimation. Of all (extra-)hypothalamic structures involved in central osmoregulation, only the MnPO revealed heat-induced Fos-IR in numerous cells located preferentially in its rostral component. Thus, the MnPO proved to be activated during both thermal and osmotic stimulations applied separately. Subjected to the combined stress (STHA-D), most brain structures investigated showed striking Fos-IR due to thermally enhanced osmotic stimulation, with additive effects demonstrated in the MnPO. The data support differential central activation of c-fos expression due to thermal or osmotic stimulations, with the MnPO acting as putative integrative center for both autonomic control circuits.

Amylin and glucose co-activate area postrema neurons of the rat

Glucose is an important metabolic factor controlling feeding behavior. There is evidence that physiologically relevant glucose sensors reside in the caudal hindbrain. The area postrema (AP) in particular, which has been characterized as a receptive site for the anorectic hormone amylin, may monitor blood glucose levels. To determine whether glucose and amylin co-activate the same subset of AP neurons, we performed extracellular single unit recordings from a rat AP slice preparation. In 53% of all AP neurons tested (n=32), the activity was positively correlated to the glucose concentration. Interestingly, there was a coincidental sensitivity (94%) of AP neurons to glucose and amylin, which exerted excitatory effects on these cells. We conclude that the co-sensitivity of AP neurons to glucose and amylin, both increasing in response to food intake, points to the AP as an important hindbrain center for the integration of the metabolic and hormonal control of nutrient intake.

Inactivation of the GR in the Nervous System Affects Energy Accumulation

The homeostatic regulation of body weight protects the organism from the negative consequences of starvation and obesity. Glucocorticoids (GCs) modulate this regulation, although the underlying mechanisms remain unclear. To address the role of central GRs in the regulation of energy balance, we studied mice in which GRs have selectively been inactivated in the nervous system. Mutant mice display marked growth retardation. During suckling age this is associated with normal fat deposition causing a 60% temporary increase of percent body fat, compared with control littermates. After weaning, fat and protein depositions are reduced so that adults are both smaller and leaner than their controls. Decreased food intake and, after weaning, reduced metabolic efficiency account for these developmental disturbances. Plasma levels of leptin and insulin, two important energy balance regulators, are elevated in young mutants but normal in adults. Leptin/body fat ratio is higher at all ages, suggesting disturbed control of circulating leptin as a consequence of chronically elevated GC levels in mutant animals. Adult mutants display increased hypothalamic CRH and NPY levels, but peptide levels of melanin concentrating hormone and Orexin A and B are unchanged. The increased levels of plasma GCs and hypothalamic CRH may act as catabolic signals most likely leading to persistently reduced energy accumulation. (Endocrinology 143: 2333–2340, 2002)

Effects of altering rostral brain stem temperature on temperature regulation in the Adelie penguin,Pygoscelis adeliae

SummaryIn 4 Adelie penguins, thermodes were implanted in the rostral brain stem. Two animals were additionally equipped with spinal canal thermodes. At thermoneutral (+ 8 to + 16°C) and cold (−18 to −22° C) ambient conditions, the effects of hypothalamic heating and cooling on the surface temperature of one flipper (skin blood flow), oxygen consumption (metabolic heat production) and esophageal (core) temperature were observed in the conscious animals.—Heating the rostral brain stem induced heat defence responses: Heat production was reduced in the cold and skin vasodilatation was evoked at thermoneutral ambient conditions. As a rule, core temperature fell during rostral brain stem heating.—Cooling the rostral brain stem did not induce clear-cut cold defence responses. On the contrary, strong cooling at thermoneutral ambient conditions induced vasodilatation in the skin. In the cold, even slight degrees of rostral brain stem cooling decreased metabolic heat production. As a rule, core temperature fell when the rostral brain stem was cooled.—It is concluded from the results that thermosensitive structures in the stimulated section of the rostral brain stem of the Adelie penguin contribute to the central temperature signal input in the range of normal to elevated core temperatures. These hypothalamic warm signals appear to be at least as effective as spinal warm signals in controlling skin blood flow and metabolic heat production. The inhibition of ongoing thermoregulatory effector activity by rostral brain stem cooling suggests positive temperature coefficients of the integrative and/or efferent neurons in the hypothalamic temperature regulation center of the Adelie penguin.

Orexin A activates leptin-responsive neurons in the arcuate nucleus

Orexins, also named hypocretins, are newly described neuropeptides, which are produced almost exclusively in neurons of the lateral hypothalamus and have been shown to increase food intake after intracerebroventricular injection. Leptin, the ob-gene product released from white adipocytes, is suspected to reduce food intake mainly by acting on neurons in the arcuate nucleus of the hypothalamus. Application of orexin A activated 85% (66 out of 78) of all neurons of the rat arcuate nucleus investigated electrophysiologically in an in vitro slice preparation, by a direct excitatory postsynaptic effect. Leptin inhibited electrical activity in 10 out of 22 orexin-sensitive neurons in this brain region and excited only 3 neurons. These data give the first indication as to where and how orexin might interact with the leptin-responsive hypothalamic network.

Salmon calcitonin – a potent inhibitor of food intake in states of impaired leptin signalling in laboratory rodents

To compare the anorectic effectiveness of leptin and the amylin analogue salmon calcitonin (sCT), rodents were treated on 1 day with subcutaneous injections. In chow‐fed C57Bl/6J mice, leptin and sCT reduced energy intake and acted additively. After C57Bl/6J mice had become leptin‐resistant on being fed chocolate as a palatable high‐caloric supplement to chow, their sCT‐induced decrease in energy intake was more pronounced than in chow‐fed mice with differential changes in the intake of chocolate (strong reduction) and chow (slight increase). Dose‐response relationships for sCT‐induced reductions in energy intake were analysed in chow‐fed C57Bl/6J mice and two obese strains, ob/ob mice and melanocortin‐4 receptor knockout (MC4‐r‐KO) mice, as well as in wild‐type and fatty (fa/fa) rats. Compared to C57Bl/6J mice, reduction in food intake induced by sCT was attenuated in MC4‐r‐KO mice, and nearly absent in ob/ob mice, over the dose range investigated. Compared to C57Bl/6J mice, wild‐type rats responded more sensitively to sCT and its efficiency was only slightly reduced in fatty (fa/fa) rats. Thus, while genetically induced failures of leptin signalling reduce the action of sCT, it effectively inhibits the intake of a palatable, high fat‐high sugar diet even in states of diet‐induced obesity with functional leptin resistance.

Thermotherapy for Neoplasia, Inflammation, and Pain

. Jpn J Hyperthermic OncoIS:51-58 13. Lithgow GJ, White TM, Melor S, et al (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by stress. Proc Natl Acad Sci USA 92:7540-7544 14. Hamet P, Sun YL, Malo 0, et al (1994) Genes of stress in experimental hypertension. Clin Exp Pharmacol and Physiol 21:907-911 15. Matsuoka H, Furusawa M, Tomoda H, et al (1995) Efficacy of indomethacine pretreatment with regional hyperthermia for treating upper abdominal malignancies. Int J Hyperthermia 11:169-171 16. Tsuji H (1996) Surgical operation and body (in Japanese). Chukoshinsho no. 1282. Chuoukoron Shinsha, Tokyo Thermotherapy of Chronic Inflammatoryl Degenerative Disease, Trauma, and Pain Clinical Usefulness of Long-Term Thermohydrotherapy (Balneotherapy)

Radioimmunoassay for arginine-vasotocin (AVT) in serum of Pekin ducks: AVT concentrations after adaptation to fresh water and salt water

A radioimmunoassay for arginine-vasotocin (AVT), the antidiuretic principle in birds, was developed using the high cross-reactivity of AVT with an AVP antiserum raised in rabbits. This assay is specific for the measurement of AVT in serum of birds. The sensitivity and precision is such that serum AVT concentrations above 0.5 fmol/ml can be measured quantitatively.A serum AVT concentration of 5.1±1.4 fmol/ml was found in normally hydrated, fresh water adapted ducks with a serum osmolality of 293.7±2.2 mosmol/kg. When the same animals were acutely hydrated, no or<0.5 fmol/ml AVT was present at an osmolality of 289.9±2.4 mosmol/kg. In salt water adapted ducks with a serum osmolality of 333.0±7.6 mosmol/kg, a serum AVT of 22.7±3.0 fmol/ml was found. When fresh water adapted ducks were hydrated and infused with different doses of AVT, a linear relationship between serum AVT and the amount infused was obtained. During AVT infusions, serum osmolality and urine flow rate were negatively correlated and urine osmolality was positively correlated with serum AVT.