Metabolic interactions between restraint stress and L-lysine: the effect on urea cycle components.

We studied the effects of L-lysine on wrap-restraint stress-induced changes in ureagenesis. An exposure to wrap-restraint stress did not affect the plasma concentration of L-lysine, but did decrease plasma urea and arginine. Oral L-lysine (1 g/kg) blocked the effect of stress on ureagenesis, and enhanced the effect of stress on L-arginine. No influence of L-lysine were found in controls. The results imply a stress-specific, ureagenesis-stimulating effect of L-lysine, and suggest an increased requirement for L-arginine during the above conditions.

Brief exposure to NaCl during early postnatal development enhances adult intake of sweet and salty compounds.

Taste acceptance involves both innate and acquired components. We observed an increased acceptance of salty and sweet solutions in adult rats whose tongues had been exposed to an NaCl-enriched milk formula during one day of early postnatal development. This behavioral effect was associated with changes in the norepinephrine system of the basolateral amygdala. No other changes in behavior, food intake, body weight, blood or metabolic parameters of the NaCl-exposed adult rats were identified. The data suggest a causal relationship between NaCl taste exposure, low content of amygdala norepinephrine cells and enhanced intake of sweet and salty compounds by adult rats. They also raise the question of the extent to which similar phenomena may occur during early human infant feeding.

Systemic administration of lentinan, a branched beta-glucan, enhances long-term potentiation in the rat dentate gyrus in vivo.

We investigated the effects of oral and intravenous application of lentinan, a branched beta-glucan, on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vivo. Oral administration of lentinan (200 mg/kg) enhanced the induction of LTP evoked by sub-threshold tetanic stimulation (20 pulses at 60 Hz) of the perforant pathway without affecting normal synaptic potentials. Intravenous injection of the compound (0.2-10.0 mg/kg) also enhanced the induction of LTP in a bell-shaped manner, whereas it had no effect on LTP evoked by supra-threshold tetanic stimulation (100 pulses at 100 Hz). Structurally related beta-glucans did not mimic the lentinan-triggered enhancement of LTP. These results suggest that peripherally applied lentinan facilitates the synaptic efficacy of the dentate gyrus neurons in vivo.

Release of hypothalamic norepinephrine during MSG intake in rats fed normal and nonprotein diet.

Effects of monosodium L-glutamate (MSG) solution (0.06 M) on interstitial levels of norepinephrine (NE) were measured in the lateral hypothalamus (LH). Wistar male rats, housed in standard operant boxes, were fed either normal or nonprotein diet for 3 days. Beside a daily bar-mediated drinking session (75 min), animals were without access to fluids. Microdialysates, collected from the LH during the 75 min of drinking, were analyzed using high-pressure liquid chromatography. No significant responses of the LH NE to the drinking of distilled water, MSG, NaCl (0.06 M), and glucose solution (0.6 M) were found in normally fed rats. However, a specific decline in LH NE release was detected during MSG solution-drinking in rats fed nonprotein diet. As MSG preference indicates protein intake, it is possible that LH NE is, at least partially, one of the brain signals that relate MSG preference to dietary protein intake.

Circadian release of hypothalamic norepinephrine in rats in vivo is depressed during early L-lysine deficiency.

Rats rapidly recognize an amino acid-deficient diet, presumably via central mechanisms that involve hypothalamic circuits. We evaluated the effects of a deficiency of the essential amino acid, L-lysine, on the ventromedial hypothalamus (VMH) norepinephrine (NE) circadian release in free-moving, nonstressed rats. A dialysis probe was implanted into the VMH of male Wistar rats. Continuous microdialysis measurement was done during the first 26 h of L-lysine (Lys) deficiency in rats that had free access to food and fluid. The dark phase was from 1900 to 0700 h. Rats were divided into six groups according to their food and fluid intakes. They were fed either normal (Lys sufficient) or Lys deficient powdered food and provided with distilled water, glycine (Gly, 400 mmol/L) or Lys solution (400 mmol/L). In control rats, VMH NE release showed a diurnal pattern, with the lowest levels measured at the onset of the dark phase. In Lys-deficient rats, the release was significantly depressed from the early morning (0500 h) compared with Lys-sufficient rats, without any differences in food and fluid intakes. A normal pattern of VMH NE was restored by the provision of 400 mmol/L Lys solution to deficient rats. The results suggest that the VMH NE release is involved in the early integration of signals about amino acid deficiency.

Effect of selected thallophytic glucans on learning behaviour and short-term potentiation.

This paper reviews the effects of thallophytic glucans on rodent cognitive performance modelled by a combination of behavioural and electrophysiological approaches. Glucans were isolated from thallophytic plants, based on prescriptions used in traditional Chinese and Japanese medicine. In parallel with the already described enhancement of hippocampal synaptic plasticity by disaccharides, polysaccharides isolated from lichens Flavoparmelia caperata and Cetrariella islandica, enhanced hippocampal plasticity and behavioural performance in rats.

Effects of L-lysine deficient diet on the hypothalamic interstitial norepinephrine and diet-induced thermogenesis in rats in vivo.

Rats readily recognize an amino acid deficient diet, presumably via central mechanisms that involve hypothalamic circuits. Presently, effects of the essential amino acid L-lysine deficiency on the ventromedial (VMH) and lateral (LH) hypothalamus norepinephrine (NE) release were evaluated in free moving rats. Microdialysis measurement was undertaken once in 48 h (12:00 noon-14:00) in rats that had free access to food and drink. Significant decline in the food intake and VMH NE release were found in rats fed L-lysine diet. No changes were identified in LH NE release. Additionally, no significant differences in diet-induced spatial thermogenesis between normal and L-lysine deficient non-stressed rats were found in vivo. The results suggested that the VMH NE release was specifically involved in the integration of signals about amino acid deficiency. However, the decrease in VMH NE was not translated into changes of thermogenic responses to diet.

Use of thermal photography to explore the age-dependent effect of monosodium glutamate, NaCl and glucose on brown adipose tissue thermogenesis.

Using a sensitive thermocamera and a hairless substrain of Sprague-Dawley rats, we developed a novel in vivo method for the evaluation of diet-induced thermogenesis. The technique enabled time-dependent monitoring of spatial heat dissipation emanating from brown adipose tissue (BAT) during diet intake. Drinking of monosodium glutamate (MSG) solution (0.12 M) enhanced standard protein (15%) diet-induced heat dissipation in young (9-12 weeks old) hairless male rats. No significant enhancement was found in 9- to 12-week-old rats that received sodium chloride (0.12 M) or glucose solution (0.6 M). The enhancing effect of MSG was age-dependent and it was not observed in 18- to 22-week-old rats due to an age-dependent decrease of thermogenic responses. No age-related changes in MSG preference or diet intake were recorded. Although it is unclear whether the effect of MSG was purely enhancing or whether the effect was independently superimposed on the diet-induced thermic activity, the results suggest that in 9- to 12-week-old rats, preference for umami taste might be associated with its enhancing effect on diet-induced thermogenesis.

Preferable Monosodium Glutamate and Sodium Chloride Solutions do not Affect Diurnal Norepinephrine Release in the Rat Lateral Hypothalamus.

Rats prefer hypo-osmolar solutions of monosodium glutamate (MSG) to water. The unique taste of MSG, called umami, has been suggested to be involved in protein homeostasis. We have investigated diurnal intake patterns of hypo-osmolar MSG solution (0.06 M) in rats fed a protein sufficient diet. Compared to water intake, animals showed a significant preference for MSG solution during the first part of dark phase (dark phase, 19:00-7:00; first part, 19:00-2:00). In contrast, no preference was found during the final part of dark phase or during light phase. No changes in food intake between the two tested groups were found. Although rats were offered MSG solution for five consecutive days, no day-to-day variations in intake were evident, suggesting that MSG preference is unlearned. Activation of the lateral hypothalamus (LH) was previously detected during of MSG solution intake in rats. Using a microdialysis technique, we evaluated LH norepinephrine (NE) release in rats drinking water, salt solution (0.06 M) and MSG solution (0.06 M). Diurnal variations of LH NE release were found in all animals without significant differences between the three groups. These data do not support involvement of LH NE in the brain recognition circuit for preferable umami or NaCl solutions.

Mineralocorticoid receptor-mediated enhancement of neuronal excitability and synaptic plasticity in the dentate gyrus in vivo is dependent on the beta-adrenergic activity.

The dentate gyrus neurons in the hippocampus contain a high density of both mineralocorticoid and adrenergic receptors. By in vivo extracellular recording from adrenalectomized rats we investigated the possible relationships between the two systems with regard to neuronal excitability and activity-dependent synaptic plasticity. Pretreatment with aldosterone significantly enhanced both basal neuronal excitability and tetanically evoked synaptic plasticity in adrenalectomized, but not sham-operated rats. The enhancement was blocked by spironolactone, indicating a mineralocorticoid receptor-dependent effect. The adrenomedullary hormone epinephrine also significantly enhanced synaptic plasticity via activation of beta-adrenergic receptors. Beta-adrenergic antagonist propranolol, infused directly into the dentate gyrus granule cell layer, significantly reduced the effect of aldosterone on neuronal excitability and partly canceled the aldosterone-enhanced synaptic plasticity. No effect of propranolol was found after its amygdaloid infusion. The mineralocorticoid receptor antagonist spironolactone did not affect the epinephrine-induced effects. These results indicate that the pretreated adrenal steroids interact with the catecholaminergic system in the dentate gyrus of adrenalectomized rats and that the functional beta-adrenergic pathway is involved in the mechanism of mineralocorticoid-induced cellular effects in vivo.

PC-2, linear homoglucan with alpha-linkages, peripherally enhances the hippocampal long-term potentiation.

PURPOSE: To investigate central effectiveness of PC-2, a glucan from lichen Parmelia caperata with alpha(1-3)(1-4) linkages in the ratio 3:2, with regard to the long-term potentiation (LTP) of evoked potential. METHODS: The extent of LTP, induced by high-frequency stimulation of medial perforant pathway, was evaluated as fractional increase in population spike amplitude in dentate gyrus in anesthetized rats. RESULTS: Oral and intravenous application of PC-2 resulted in significant enhancement of LTP elicited by a weak, but not by a strong, tetanic stimulation. No influence of PC-2 on basal evoked synaptic potential was found. Bilateral adrenalectomy profoundly suppressed the positive impact of the glucan on the formation of LTP, but showed no effect upon the magnitude and time-course of population spike enhancement in vehicle-treated subjects. Two related alpha-glucans with different chemical structures did not show any effect comparable to that of PC-2. CONCLUSIONS: Peripheral application of PC-2 significantly enhances LTP in dentate gyrus in rats. Results indicate that the effect of PC-2 might be peripherally mediated and that the specific higher structure of PC-2 is crucial for its biological activity.

Hippocampal long- and short-term potentiation is modulated by adrenalectomy and corticosterone.

The effect of acute corticosterone (CORT) treatment on elaboration of long-term potentiation (LTP) and short-term potentiation (STP) in intact and adrenalectomized rats was investigated. Both forms of synaptic plasticity were evaluated as fractional increases in population spike amplitude in dentate gyrus granule cells following brief, high-frequency stimulation of the medial perforant pathway in vivo. LTP was distinguished from STP by the magnitude and time course of population spike facilitation. Adrenalectomy resulted in profound reduction of LTP extent, without any significant effect upon STP. Replacement of glucocorticoid by a single injection of CORT to previously adrenalectomized rats restored LTP to control levels. When CORT was applied to intact subjects, it slightly, but significantly, impaired LTP development. No effect of CORT on STP induction and time course was found. Taken together, these results show that the modulation of synaptic efficiency in hippocampal dentate gyrus by circulating glucocorticoid depends on the form of plasticity examined. LTP was found to be more susceptible to the impairment induced by both high and low levels of glucocorticoid than STP.

Interaction of adrenocorticotropin-(1-24)-tetracosapeptide with lipid bilayers.

The interaction of the peptide hormone adrenocorticotropin with solvent-free planar lipid bilayers (BLM) and liposomes was studied by measurements of elasticity modulus perpendicular to the plane of the membrane (E perpendicular, measured by electrostriction), surface potential difference (delta phi m), electrical capacitance, capacitance relaxation following a voltage jump (yielding relaxation times for molecular dipoles or dipolar domains), and fluorescence polarization. Addition of the 6-fold positively charged peptide to one side of the membrane leads to a more positive membrane surface potential, an increase of BLM capacitance, a decrease of elasticity modulus, and faster relaxation time constants. This also caused a decrease of DPH fluorescence anisotropy of the liposome suspension modified by fluorescent dye DPH. Mixed BLM of palmitoyl-oleoyl-phosphatidylcholine (POPC)+soybean phosphatidylcholine (SBPC) (10:1 w/w), which carry a negative surface charge, exhibit considerably larger changes than electroneutral POPC membranes. Our results confirm that ACTH1-24 binds to BLM and interacts with the hydrophobic part of the bilayer.

Hoelen (Poria Cocos Wolf) and ginseng (Panax Ginseng C. A. Meyer), the ingredients of a Chinese prescription DX-9386, individually promote hippocampal long-term potentiation in vivo.

DX-9386 is a traditional Chinese medicinal prescription consisting of ginseng (Panax Ginseng C. A. Meyer), polygala (Polygala Tenuifolia Willdenew), acorus (Acorus Gramineus Soland) and hoelen (Poria Cocos Wolf). We recently found that oral administration of the prescription at a dose of 500 mg/kg intensified the formation of long-term potentiation (LTP) in the dentoff gyrus of anesthetized rats. To evaluate the individual contribution of separate ingredients in DX-9386 towards the observed biological activity, we investigated their direct influence upon LTP formation in vivo. A single oral administration of hoelen and ginseng (250 and 500 mg/kg) significantly increased the spike amplitude evoked by a subthreshold tetanic stimulation at time intervals up to 30 min after tetanus. Only minor effects of polygala (500 mg/kg) and no influence of acorus up to 500 mg/kg were observed. No drugs affected the basal spike amplitude induced by a test stimulus. In addition, we ascertained that DX-9386 was also active at a dose of 250 mg/kg. Taken together, these results indicate that hoelen and ginseng are the active components of DX-9386 with regard to the enhancement of hippocampal LTP.

Influence of salmon melanin concentrating hormone on vasopressin analogue (dDAVP) activity and sodium transport in frog skin.

Salmon melanin-concentrating hormone (sMCH) is a peptide known to regulate skin pigmentation both in fish and tetrapod (frog and lizard). To evaluate the influence of sMCH on ionic transport in frog skin, standard voltage-clamp technique for the measurement of transepithelial short-circuit current (ISC) reflecting net sodium transport was used. It was found that sMCH alone applied at concentrations of 0.5; 5 or 10 mumol/l failed to influence ISC. The application of 5 mumol/l of sMCH, however, inhibited ISC across the skin stimulated by a synthetic analogue of vasopressin (dDAVP), whereas no influence on natriferic effect of 1 mumol/l forskolin by the studied peptide was observed. The results indicate that cAMP was presumably not involved in the mediation of sMCH action in frog skin. We assume that the interaction of sMCH with the basolateral membrane could lead either (1) to changes of membrane structure including organization of its lipid surrounding or (2) to modification of AVP/dDAVP receptor activity and binding capacity. The nature of these interactions and change(s) in cell membrane and signal(s) which trigger processes responsible for the inhibitory effect of sMCH on dDAVP-stimulated frog skin sodium transport remains to be elucidated.