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Long-term potentiation (LTP) and long-term depression represent important processes that modulate synaptic transmission that carries out a key role in neural mechanisms of memory. Many studies give strong evidences on a role of the reactive oxygen species in the induction of LTP in CA1 region of hippocampal slices that was inhibited by adding the scavenger enzyme superoxide dismutase (SOD1). Previous data showed that SOD1 is secreted by many cellular lines, including neuroblastoma SK-N-BE cells through microvesicles by an ATP-dependent mechanism; moreover, it has been shown that SOD1 interacts with human neuroblastoma cell membranes increasing intracellular calcium levels via a phospholipase C-protein kinase C pathway activation. The aim of this study was to investigate the effect of intracerebral injection of SOD1 or the inactive form of enzyme (ApoSOD) on the modulation of synaptic transmission in dentate gyrus of the hippocampus in urethane anesthetized rats. The results of the present research showed that intracerebral injection of SOD1 and ApoSOD in the dentate gyrus of the rat hippocampal formation inhibits LTP induced by high-frequency stimulation of the perforant path. This result cannot be only explained by the dismutation of oxygen radical induced by SOD1 since also ApoSOD, that lacks the enzymatic activity, carries out the same inhibitory effect on LTP induction.

The mechanisms of tolerance to subsequent episodes of ischemia induced by cortical spreading depression (CSD) are not clear. The effects of CSD on the expression of inducible nitric oxide synthase (iNOS), hypoxia inducible factor-1 alpha (HIF-1 alpha), and lactate dehydrogenase-A (LDH-A) were evaluated in the present experiment. Unilateral CSD was induced in Sprague-Dawley rats by application of KCl on the right cortex and the mRNA levels of iNOS, HIF-1 alpha, and LDH-A were evaluated at 15 min, 2 h, 4 h, 6 h or 24 h after CSD. RT-PCR analysis showed: 1) an increase of MOS mRNA at 15 min, 2 h, 4 h; 2) an increase of HIF-1 alpha mRNA at 6 h; 3) an increase of LDH-A mRNA at 4 h. In situ hybridization with specific digoxigenin-labeled oligonucleotides revealed that the mRNA levels were increased at 15 min-2 h for MOS, 2-4 h for LDH-A and 6 h for HIF-1 after CSD. Immunohistochemistry analysis revealed that levels of iNOS and HIF-1 alpha were increased, respectively, at 2 h and 6 h after CSD. These data suggest that CSD promotes the expression of iNOS, HIF-1 alpha, and LDH-A in nervous cells giving a neuroprotective effect. (C) 2008 Published by Elsevier Ltd on behalf of IBRO.

During childhood and adolescence, a game could be an effective educational tool to learn healthy eating habits. We developed Kaledo, a new board game, to promote nutrition education and to improve dietary behavior. A two-group design with one pre-treatment assessment and two post-treatment assessments was employed. A total of 3,110 subjects (9-19years old) from 20 schools in Campania, Italy, were included in the trial. In the treated group, the game was introduced each week over 20 consecutive weeks. Control group did not receive any intervention. The primary outcomes were (i) score on the "Adolescent Food Habits Checklist" (AFHC), (ii) scores on a dietary questionnaire, and (iii) BMI z-score. At the first post-assessment (6months), the treated group obtained significantly higher scores than the control group on the AFHC (14.4 (95% confidence interval (CI) 14.0 to 14.8) vs 10.9 (95% CI 10.6 to -11.2); F(1,20) = 72.677; p

Introduction: Prevention of obesity and overweight is an important target for health promotion. Early prevention requires an intervention during childhood and adolescence. At these stages, the game could be an appropriate means to teach nutrition knowledge and to influence dietary behaviour. To this end, the authors developed Kaledo, a new board-game. Objective: The aim of the present study was to test the efficacy of Kaledo on changes in nutrition knowledge and dietary behaviour in a pilot study conducted in three middle schools in Naples, Italy. Materials and Methods: A simple two-group design (treatment and control) with pre- and post-assessment was employed. The classroom was the unit of recruitment and random assignment to groups. All students (307) in the participating schools were invited to participate. Data analysis was performed on 241 subjects. During 24 weeks, a group of 153 children from 8 classrooms (11-14 year old Caucasian subjects; 78 male, 75 female) was involved in 15-30 minute-long play sessions once a week. A questionnaire was given to the participants at the beginning and at the end of the study to evaluate nutrition knowledge (31 questions), physical activity (8 questions) and food intake (34 questions). Anthropometric measurements were also carried out. A second group of 88 children from 5 classrooms (same age and ethnicity; 55 male, 33 female) was investigated at the same times with the same questionnaire and anthropometric measures but they did not receive any play sessions with Kaledo. Observation: Children playing Kaledo showed a significant increase in nutrition knowledge (p < 0.05) and in weekly vegetable intake (p < 0.01) with respect to the control. Conclusion: The results suggest that Kaledo could be an effective instrument to teach children about healthy diet. More research is needed to study the long term effect of this intervention.

Asymmetrically placed visual distractors are known to cause a lateral bias in the execution of a movement directed toward a target. The aim of the present experiment was to verify if the trajectory of the ball and the trajectory of the jump for a basketshot can be affected by the sole position of a second player, who stays in front of the shooting player in one of three possible positions (centre, left or right) but too far to physically interfere with the shot. Young basketball players were asked to perform 60 shots at 6.25 m from a regular basket, with or without a second player staying in front of them in, alternately, a centre, left or right position. A computerised system measured the angular deviation of the jump direction from the vertical direction and the lateral deviation of the ball trajectory from the midline. The results showed that both the jump direction and the entry position of the ball deviated toward the opposite side from the second player’s side; however, these effects were too small to significantly affect the mean goal percentage. This result confirms that some placements of the players can have an effect as visual distractors. Further studies are necessary to find what game conditions can make such distractors harmful for the athletic performance.

Cortical spreading depression (CSD) enhances ischemic tolerance to temporary focal ischemia. Although this effect most likely requires the expression or activation of neuroprotective factors, their identity remains relatively unknown. One important factor involved in neuroprotection is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase that is activated via phosphorylation. This activation occurs in response to brain ischemia, hypoxia, or glucose deprivation. Thus, to determine the potential mechanism of the neuroprotective effects of CSD, we tested whether AMPK becomes phosphorylated into phospho-AMP-activated protein kinase (pAMPK) after CSD. CSD was induced for 15 min in three groups of five rats. The animals were subsequently sacrificed after 2, 4 or 24 h. Western blot analyses were performed to determine the AMPKα and pAMPKα levels in the cortex (right and left hemispheres), and immunohistochemistry and immunofluorescence were performed to determine the localisation of AMPKα and pAMPKα in the cerebral cortex. These results demonstrated a significant increase in pAMPKα at 24 h (but not at 2 and 4 h) after CSD. In contrast, un-phosphorylated AMPK expression did not change. The increase in pAMPKα was confined to neurons (predominantly neurons located in the superficial layers of the cerebral cortex) and was not observed in astroglial cells. Taken together, these data indicate that AMPK is activated by CSD, and suggest that this activation may contribute to the neuroprotective effect of CSD.

This study showed that citiolone (CIT), a free radical scavenger, significantly increased superoxide dismutase (P < 0.001 vs. untreated NOD, NMMA-treated, and silica-treated animals), catalase (P < 0.01 vs. untreated NOD), and glutathione peroxidase (P < 0.001 vs. untreated NOD and C57BL6/J) values. Silica treatment was capable of counteracting the plasma antioxidant capacity (TRAP) decrease observed in untreated NOD mice, although it did not block the blood glucose rise and insulitis progression in type 1 diabetes significantly. Conversely, early silica administration was able to deplete macrophages (as demonstrated by immunocytochemistry) and to block the rise in blood glucose levels and insulitis progression significantly. Silica-treated animals in this study showed the highest TRAP levels, demonstrating that depletion of macrophages also was able to improve the antioxidant status. This study suggested that macrophages are essential for type 1 diabetes development and showed that they also are involved when the antioxidant status is affected. The reported findings are significant in view of previous studies indicating that oxygen and/or nitrogen free radicals contribute to the islet beta-cell destruction in type 1 diabetes animal models.

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT) and IBAT and colonic temperatures (T IBAT and T c ) were monitored in urethane-anaesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a 4 μmoles l -arginine ( l -arg) or 400 nmoles nitroprusside (NP) injection in a lateral cerebral ventricle and an intracerebroventricular administration of 500 ng prostaglandin E 1 (PGE 1 ). The same variables were monitored in other rats with l -arg or NP or PGE 1 administration alone. No drug was injected in control rats. The results show that l -arg or NP injection reduces the increases in firing rate, T IBAT , T c induced by PGE 1 These findings suggest that nitric oxide is important in the control of thermogenic changes during the PGE 1 hyperthermia.

Diets high in methionine lead to elevation of plasma homocysteine levels which are possibly linked to neurodegenerative diseases and oxidative stress. In the present study, we investigated the effects of methionine-enriched diet on antioxidant defences, on rat spontaneous behaviour and on the ability to sustain long-term potentiation in the dentate gyrus (DG). Sprague-Dawley rats were fed either a standard laboratory diet or a methionine enriched-diet (1% or 5% methionine in drinking water) for 8 weeks. After the 8 weeks, the animals were tested for spontaneous motor activity and habituation in an open field maze, for anxiety-like behaviour in an elevated plus maze and for the ability to sustain long-term potentiation (LTP) induced in the dentate gyrus under urethane anaesthesia. The brains were then removed and histochemically stained for superoxide dismutase (SOD) activity. Rats fed on 5% methionine significantly reduced total distance travelled during the open field test and exhibited no habituation with respect to the other two groups. Rats fed on 5% methionine also showed a significant increase of the anxiety level. Moreover, in this group, the ability to induce LTP in DG was impaired. SOD activity was significantly increased in the cerebral cortex of the rats fed on 1% and 5% methionine with respect to the control group. In conclusion, 5% methionine in drinking water led to evident impairment of locomotor skills and of synaptic plasticity. SOD activity in the cortex was increased in both the groups fed on 1% and 5% methionine, thus suggesting that metabolic adjustments, triggered by the methionine-enriched diet, are likely mediated by reactive oxygen species. Diets high in methionine lead to elevation of plasma homocysteine levels which are possibly linked to neurodegenerative diseases and oxidative stress. In the present study, we investigated the effects of methionine-enriched diet on antioxidant defences, on rat spontaneous behaviour and on the ability to sustain long-term potentiation in the dentate gyrus (DG).Sprague-Dawley rats were fed either a standard laboratory diet or a methionine enriched-diet (1% or 5% methionine in drinking water) for 8 weeks. After the 8 weeks, the animals were tested for spontaneous motor activity and habituation in an open field maze, for anxiety-like behaviour in an elevated plus maze and for the ability to sustain long-term potentiation (LTP) induced in the dentate gyrus under urethane anaesthesia. The brains were then removed and histochemically stained for superoxide dismutase (SOD) activity.Rats fed on 5% methionine significantly reduced total distance travelled during the open field test and exhibited no habituation with respect to the other two groups. Rats fed on 5% methionine also showed a significant increase of the anxiety level. Moreover, in this group, the ability to induce LTP in DG was impaired. SOD activity was significantly increased in the cerebral cortex of the rats fed on 1% and 5% methionine with respect to the control group.In conclusion, 5% methionine in drinking water led to evident impairment of locomotor skills and of synaptic plasticity. SOD activity in the cortex was increased in both the groups fed on 1% and 5% methionine, thus suggesting that metabolic adjustments, triggered by the methionine-enriched diet, are likely mediated by reactive oxygen species. (c) 2012 Elsevier B.V. All rights reserved.

We have tested the hypothesis that there is a role for the cerebral cortex in the control of non-shivering thermogenesis during fever induced by prostaglandin E1 (PGE1). While under urethan anesthesia, the firing rate of nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc) and oxygen (O2) consumption were monitored during the fever from PGE1 injection (400 and 800 ng) in a lateral cerebral ventricle in controls and in functionally decorticated Sprague-Dawley rats. Rats were functionally decorticated by applying 3.3 M KCl solution on the frontal cortex which causes cortical spreading depression (CSD). Pyrogen injections caused dose-related increases in firing rate, TIBAT, Tc and O2 consumption and CSD reduced these enhancements. Our findings indicate that the cerebral cortex could be involved in the control of non-shivering thermogenesis during PGE1-induced febrile response.

Cortical spreading depression (CSD) is a reversible electrophysiological phenomenon that is not associated with tissue damage under normal blood supply. The induction of CSD during ischemia causes an increase in tissue damage, while pre-conditioning with CSD decreases the damage induced by a subsequent episode of ischemia. The mechanisms underlying these effects are not clear. Because the production of reactive oxygen species (ROS) is involved in tissue damage during ischemia-reperfusion, the aim of the present study was to evaluate the effects of CSD on superoxide production (O(2)(-)), on hydrogen peroxide (H(2)O(2)) production and on superoxide dismutase (SOD) activity in the cerebral cortex. CSD was induced by KCl application on the cortical surface in rats. O(2)(-) production was evaluated using dihydroethidium (DHE) that is oxidized to the fluorescent dye ethidium (HEt) by O(2)(-). The extracellular level of H(2)O(2) was evaluated by microdialysis sampling and HPLC analysis. SOD activity was evaluated with a histochemical assay. The results showed an increase in H(2)O(2) production, an increase in SOD activity and a decrease in O(2)(-) concentration 1h after CSD induction.

Octylphenol (OP) is an endocrine-disrupting chemical that accumulates in various organs. It has also been shown to exert noxious effects on the central nervous system. In the present study, we measured in Sprague–Dawley rats the degree of OP accumulation in different areas of the brain and investigated the effect of OP in pain modulation. Two groups of male Sprague–Dawley rats were treated for 20 days with 50 mg/kg BW/day of OP (group 1) or vehicle (group 2). At the end of the treatment, the formalin test was performed to evaluate the effect of OP exposure on pain. Soon after, rats were sacrificed, and the accumulation of OP in the cerebral cortex, hippocampus, hypothalamus, cerebellum, thalamus, striatum, mesencephalus and ventral hindbrain was measured by HPLC analysis. The results showed a greater accumulation of OP in the cerebral cortex compared to all the other areas; there was also more accumulation in the cerebellum compared to the mesencephalus and thalamus. No accumulation was found in the striatum. These results suggest that there is a preferential accumulation of OP in different areas of the brain with consequences to neural behaviour. On the contrary, experiments on facial grooming did not show significant effects of OP on pain.

The aim of the present study was to evaluate the production of superoxide anion (O(2)(-)) in the trigeminal complex nuclei after a functional mechanical overload of the teeth due to the preference for masticating on one side in rats. The preference for masticating on one side was induced by the discomfort due to a small abrasion of one molar; such lateralisation in mastication was confirmed by electromyography. The production of O(2)(-) was evaluated in the trigeminal nuclei by fluorescence microscopy after an injection of dihydroethidium. The results showed that there was an increased production of O(2)(-) in the subnucleus oralis of the spinal trigeminal nucleus in the same side where the mastication was preferred. This result demonstrates that an increased activity of non-painful sensory neurons can enhance the production of reactive oxygen species within the central second order sensory nuclei. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

MyoD is a myogenic regulatory factor with a critical role in skeletal muscle development and regeneration. As muscle regeneration comes with an inflammatory process, it has been proposed that the inflammatory cells can play an important role in the induction of muscle fibres regeneration. The aim of the present work was to verify if a cyclooxygenase inhibitory drug (ketoprofen) would alter the normal expression of MyoD in a regenerating rat soleus muscle after an over-load lesion. Using immunohistochemical techniques, the numbers of m-cadherin-positive cells, a selective marker of satellite cells, and MyoD-positive cells were evaluated in functionally overloaded rat soleus muscles 4 days after a gastrocnemius tendon cut. The same study was conducted either with four rats injected with ketoprofen (100 mg/kg b.w./day) or with four rats injected with saline solution. The data obtained showed a very large decrease in the number of MyoD positive/m-cadherin positive cells in the ketoprofen injected group compared to the control group. Although further studies are needed to elucidate the sequence of biochemical events that induce a reduction of MyoD expression due to ketoprofen, the results demonstrate that prostaglandin synthesis is required for the induction of MyoD expression and that ketoprofen can affect this expression, with possible adverse effects on muscle regeneration.

Caffeine induces modifications of activity of the autonomic nervous systems This study analyzed the effect of a cup of espresso coffee on the heart rate variability m (HRV) power spectral analysis, which is a method providing evaluation of the sympathetic and parasympathetic discharges In young, healthy sedentary subjects (10 male, 10 female; aged 25-30 years), the HRV-power spectrum was evaluated over a period of 150 min after the administration of espresso coffee (caffeine, 75 mg) or decaffeinated coffee (caffeine, < 18 mg) in supine and seated positions Absolute values of the spectrum were summed in low m (LF) and high frequencies m (HF). The LF and HF spectra were used to estimate the sympathetic and parasympathetic activity, respectively. In the supine position, coffee increases HF, while decaffeinated coffee causes little modifications of HF. In the seated position, HF is not modified by coffee or decaffeinated coffee. Coffee and decaffeinated coffee do not induce any modification of LF in both positions. This experiment indicates that espresso coffee influences parasympathetic activity in the supine positions

The aim of the present preliminary study wets to describe a simple protocol for the analysis of the heart rate variability (HRV) that can reveal the different autonomic control between noncomplicated diabetic patients and normal subjects within 15 min. The power spectrum of the HRV was evaluated on 5-min-long electrocardiographic recordings in both the supine and the seated positions in 30 non-complicated noninsulin-dependent diabetic (NIDDM) patients and in 30 healthy volunteers. In healthy subjects the low-frequency (LF) value was higher in seated position than in supine position, while in diabetic patients the LF value in seated position did not differ from that in supine position and did not differ from that in healthy subjects in supine position. The present work demonstrates that the protocol described reveals a different autonomic regulation of the heart rate in healthy subjects and in NIDDM patients even if there is no clinically evident autonomic neuropathy. (C) 2009 Elsevier Inc. All rights reserved.

The impairment of brain functions during aging could be prevented by an increase in antioxidative defenses. In fact, dietary manipulation with antioxidants or with antioxidant-rich extracts from vegetables and fruit can ameliorate age-associated behavioral alterations. Moreover, dietary supplements of antioxidants can reverse the age-dependent impairment to sustain long-term potentiation (LTP). There is evidence that fresh fruit could be more effective than antioxidant supplements or fruit and vegetable extracts but the effect of a diet enriched in fresh fruit on brain aging process has not been investigated until now. The aim of the present study was to verify whether dietary manipulation with fresh apples could influence age-induced changes in motor and emotional behavior and in LTP in rats. Groups of aged and young rats were fed with a standard diet or a diet supplemented with fresh apples of annurca variety for 10 weeks and assessed for behavioral performance in the open field and elevated plus maze tests and for the ability to sustain LTP. The brains were then removed, histochemically stained for superoxide dismutase (SOD) and SOD activity was measured by computer-assisted image analysis. The aged rats fed with the enriched diet showed a significant decrease in the anxiety level. Moreover, they improved in the ability to sustain LTP, reaching the level of the young rats. SOD activity was increased in the aged rats fed with the standard diet whereas SOD activity in the hippocampus of the aged rats treated with annurca apple was at the level of the young animals. These results suggest that a diet rich in annurca apple could have an important role in health-care during aging.

Aim: Hypocretin 1 is an hypothalamic neuropeptide that induces an increase in food intake when administered into the cerebral lateral ventricle. As it is well known that the medial hypothalamus (MH) is involved in the feeding behaviour also through GABAergic circuits, the aim of this experiment was to investigate the effect of an hypocretin 1 intracerebroventricular (icv) injection on the extracellular levels of GABA in the MH. Methods: GABA levels in the MH were evaluated in six rats by microdialysis and high performance liquid chromatography-electrochemical detection 30 min before and every 30 min for an over all period of 6 h after an icv injection of hypocretin 1. The same procedure was used in another group of six rats but saline was injected into the lateral ventricle as control. Results: The results show that extracellular GABA increases in the MH after the injection of hypocretin 1 at 60 min and at 3 h after the injection. Conclusion: This finding suggests a possible mechanism by which hypocretin 1 should induce hyperphagia in the first hour after injection. As it is already known that the inhibition of the MH by injection of GABA causes an increase of food intake, it is possible that hypocretin 1 causes an increase in food intake by increasing the GABA release in the MH. The lack of an increase in the GABA level after the fourth hour is consistent with the lack of an increase in food intake at this time, as we observed in previous experiments. The finding of a biphasic increase in the GABA level, at 60 min and at 3 h, was unexpected and should be further investigated.

We investigate the role played by dendritic cells (DCs) in the non-obese diabetic (NOD) mouse pancreas. The early peri-islet, nondestructive infiltration phase, and intra-islet, destructive infiltration phase, which immediately precedes overt diabetes, are studied. Results show that infiltrating cells are Ia-b, ICAM-1, and, mainly, MIDC-8 immunoreactive (ir). These data from silica-treated animals and ultrastructural observations strongly support the hypothesis that DCs are both Ia-b-ir and ICAM-1-ir and that they exert a pivotal role during the period of early infiltration. This is a novel finding for NOD mice and increases the interest for this protective cell type during the rather complex islet infiltration process. Moreover, the cytokine profile demonstrates that Th2 protective cytokines are specific for peri-islet infiltrate. Disappearance of DCs from the infiltrate is concomitant with both the formation of intra-islet infiltration and the increase in proinflammatory Th1 cytokine levels. This further supports the hypothesis that DCs may exert a protective role against diabetes development.

The aim of this experiment was to evaluate the effects of ventromedial hypothalamus lesions on the thermogenic changes that follow food intake. Four groups of six Sprague-Dawley male rats were used. Under anesthesia with pentobarbital, the animals in the first and second groups received lesions at the ventromedial hypothalamus, and animals in the third and fourth groups received sham lesions. Body weight and food intake were monitored daily until the experimental procedure began. Twenty days after lesion, oxygen consumption, firing rate of sympathetic nerves to interscapular brown adipose tissue (IBAT), and IBAT temperature were monitored for 45 min both before and after 5 g food intake in 24 h fasted rats from the first and third groups. The same variables were measured in the animals of the second and fourth groups 50 days after receiving the lesions. Lesion placements were histologically verified. The results showed that lesions produced hyperphagia and obesity. Firing rate of nerves to IBAT, IBAT temperature, and oxygen consumption increased after food intake in sham-lesioned rats. This increase was significantly reduced by the lesion at both the 20- and 50-day time points. These findings indicate that the ventromedial hypothalamus controls postingestional activation of sympathetic discharge to IBAT. The reduction of postingestional thermogenesis could be involved in the development of obesity induced by lesion of the ventromedial hypothalamus.

This experiment tests the effect of intracerebroventricular (icv) injection of lysine acetylsalicylate on the sympathetic and thermogenic changes induced by lesion of the lateral hypothalamus (LH). The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures (T IBAT and T c ) were monitored in urethane-anaesthetized male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after an icv injection of Img lysine acetylsalicylate. The same variables were also monitored in: a) lesioned rats with icv administration of saline; b) sham-lesioned animals with icv injection of lysine acetylsalicylate; c) sham-lesioned rats with icv injection of saline. In an additional experiment, the same variables were monitored after an icv injection of lysine acetylsalicylate or saline in rats with LH lesion performed 48 h before the icv injection. The results show that lysine acetylsalicylate injection reduces the increases in firing rate, T IBAT , and T c induced by LH lesion. These findings suggest that cerebral prostaglandin synthesis plays a key role in the sympathetic and thermogenic changes following LH lesion.

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and Tc), heart rate, and oxygen (O2) consumption were monitored in urethane-anesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a 56 ng muscimol injection in the posterior hypothalamus and an intracerebroventricular administration of 500 ng prostaglandin E1 (PGE1). The same variables were monitored in other rats with muscimol injection or PGE1 administration alone. No drug was injected in control rats. The results show that muscimol injection reduces the increases in firing rate, TIBAT, Tc, heart rate, O2 consumption induced by PGE1. These findings suggest that GABAergic tone in the posterior hypothalamus is important in the control of thermogenic changes induced by PGE1.

Postprandial thermogenesis is under the control of the autonomic nervous system and alimentary conditioned stimuli change sympathetic and parasympathetic activity. Here we studied the effect of conditioned taste aversion on postprandial thermogenesis in rats. Two groups of animals were used, rats of the first group were controls, these were placed on a standard diet and, for some days, on two other different diets: one thiamine-free and the other thiamine-rich. Each diet had a different taste. The treated animals belonged to the second group, these were fed with the same three diets but for different lengths of times: thiamine-free diet for the first 5 wk afterwards, with thiamine-rich diet for 3 wk, and finally with laboratory standard diet for a few days. After a preference test with the three familiar diets, oxygen consumption rate and brown adipose tissue temperature were evaluated three times in both groups after ingestion of a test meal, each time with one of the three different diets. The preference test was unvaried for the three different familiar foods in controls, while the treated animals showed a lower preference for thiamine-free food than for the other two. Treated rats had a significantly higher increase in O 2 consumption rate than controls. In this group intake of thiamine-free food induced a significantly lower increase in O 2 consumption than the other two. The increase in brown adipose tissue temperature was also higher in treated than in control animals but in treated rats this was lower after intake of thiamine-free food than after the intake of the other two. The higher rise in postprandial thermogenesis in treated rats and the lower response found after intake of an aversive meal is probably due to changes in the autonomic nervous and of endocrine systems.

THE firing rate of the posterior hypothalamic neurones and interscapular brown adipose tissue and colonic temperatures (T IBAT and T C ) were monitored in 36 urethaneanaesthetized male Sprague-Dawley rats before and after an intracerebroventricular (i.c.v.) injection of 400 ng prostaglandin E 1 (PGE 1 ) or saline. The i.c.v. injection was preceded by functional decortication in half of each group. The results show an increase of firing rate, T IBAT and T C after PGE 1 injection in the rats without decortication. Functional decortication significantly reduced these enhancements. These findings demonstrate that the posterior hypothalamus plays a significant role in the hyperthermia induced by PGE 1 and that the cerebral cortex is involved in the control of posterior hypothalamic activity

The experiment described here tests the effect of intracerebroventricular (icv) injection of nitric oxide (NO) precursors, such as L-arginine (L-arg) and nitroprusside (NP), on the thermogenic changes induced by lesion of the lateral hypothalamus (LH). The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures (TIBAT and TC) were monitored in urethane-anesthetized male Sprague-Dowley rats lesioned in the LH. These variables were measured before and after and icv injection of 4 μmol L-arg or 400 nmol NP. The same variables were also monitored in: a) lesioned rats with icv administration of saline; b) sham-lesioned animals with icv injection of L-arg or NP; c) sham-lesioned rats with icv injection of saline. The results show that L-arg or NP injection reduces the increases in firing rate, TIBAT, and TC induced by LH lesion. These findings suggest that NO plays a key role in the thermogenic changes following LH lesion.

Chronic electroconvulsive shock (ECS) has been previously reported to blunt the melatonin response to acute isoproterenol administration in rats. To assess whether electrically induced seizures are indeed required for the appearance of the blunted pineal response to isoproterenol, pineal and serum melatonin levels were measured after isoproterenol stimulation in rats treated with ECS (80 mA, 0.5 sec), subconvulsive shock (15 mA, 0.5 sec), or sham-ECS once per day at 11:30-12:00 h for 8 days. In ECS-treated rats, both pineal and serum melatonin levels after isoproterenol administration were significantly lower than those in sham-treated animals and in rats receiving subconvulsive shock. Moreover, as compared with sham treatment, chronic subconvulsive shock did not affect the melatonin response to isoproterenol. These data show that seizure activity is indeed required for the ECS-induced decrease in the pineal response to acute β-adrenergic stimulation.

The effects of a hypothalamic ventromidial area lesion on energy balance were tested in exercising rats and in sedentary rats to add further information about the type of obesity developed after ventromedial lesion. Four groups of six male Sprague-Dawley rats were used. Group 1: sham-lesioned and sedentary rats, which were utilized as control rats (C); group 2: sham-lesioned and exercising rats (E); group 3: lesioned and sedentary rats (L); group 4: lesioned and exercising rats (LE). The exercise consisted of daily swimming for 30 min. Resting oxygen consumption, food intake, and body weight were measured before any treatment and 3 weeks after the lesion or/and the exercise period. The results showed that the oxygen consumption increased in the E and LE groups but not in the C and L groups. Food intake increased more in E and LE groups than in L group. The increases in body weight were higher in L and LE than in the E and C groups. These findings suggest that exercise modifies resting oxygen consumption and food intake in lesioned rats, but does not influence the degree of obesity. Thus, the ventromedial syndrome can be considered a type of obesity not completely unregulated.

Chronic electroconvulsive shock (ECS) has been shown to induce a downregulation of beta 1-adrenergic receptors in the rat cerebral cortex. Because the secretion of melatonin in the pineal gland is regulated primarily by beta 1-adrenoceptors, in the present study we investigated the effect of chronic administration of ECS on pineal beta-adrenergic responsiveness to isoproterenol. To this purpose, young adult male rats received once daily for 8 days ECS (80 mA, 0.5 s) or sham ECS. On the day after the last ECS or sham treatment, they were injected with isoproterenol hydrochloride (1 mg/kg SC) or volume-matched saline at 1600 h. Two hours later they were killed by decapitation. Results showed that the isoproterenol-induced increase in the pineal melatonin content was blunted in rats treated with ECS as compared to sham-treated animals (shock x drug interaction = p < 0.01). These data indicate that chronic ECS treatment affects beta 1 receptor-mediated melatonin production in the pineal gland. Further studies need to elucidate whether the blunted melatonin response to isoproterenol in ECS-treated rats is due to a downregulation of pinealocyte beta-adrenergic receptors.

The effects of electrolytic lesions in the hypothalamus paraventricular nucleus were studied in adult male and female Sprague-Dawley rats, fed different diets, consisting of either palatable human food plus chow (cafeteria diet) or chow alone. The results showed that both cafeteria diet and lesions induced an increase in energy intake and weight gain in rats of both sexes. Oxygen consumption rate and colonic temperature were significantly decreased by lesions, while cafeteria diet increased the same parameters only in intact animals. The lesion decreased weight, protein and DNA, and temperature of brown adipose tissue, while cafeteria diet increased the values considered in brown adipose tissue of sham-injured rats, but not in lesioned animals. The response to norepinephrine administration was significantly greater in intact rats and those fed cafeteria diet. The results suggest that the larger body weight gain observed in lesioned rats, particularly evident in rats fed cafeteria diet, is partly due to the disappearance of diet-induced thermogenesis that depends on the reduced mass and functional activity of brown adipose tissue.

Oxygen consumption, colonic and interscapular brown adipose tissue temperature were evaluated in four groups of male and four groups of female rats both before and after lesions in different brain regions, and following β-blocker propranolol administration. Recovery of body weight with varying difficulties in reaching food was also recorded in the injured animals. Groups consisted of rats with bilateral lesions in the entopeduncular nucleus (group EN), rats with bilateral lesions in the globus pallidus (group GP), rats with lateral hypothalamic lesions in the left side and entopeduncular lesion in the right side (group EN-LH), and rats with bilateral lesions in the lateral hypothalamus (group LH). Colonic and brown adipose tissue temperature and oxygen consumption were significantly increased after lesions in rats of groups EN, LH and EN-LH, but not in animals of the GP groups. Similarly, propranolol administration blocked the rise in heat production only in EN, LH and EN-LH animals. No differences were found between sexes. The survival rate was the same in all groups. GP rats recovered body weight earlier than animals injured in the other regions. The difficulty in reaching food was an important factor only in rats damaged in the EN. The results suggest that lateral hypothalamus and entopeduncular nucleus share a common regulatory function of the energy metabolism, while EN lesions induce a motor deficit in addition.

Three different techniques of total body washout (T.B.W.) have been used in experiments dealing with rats. The first technique was employing inferior vena cava as input and abdominal aorta as output; the second one performed just the opposite way; finally the third used abdominal aorta at the start of the experiment, whereas inferior vena cava was selected at the end. The last one proved to be the most efficient technique in comparison to the other ones.

Functional ablation of the cerebral cortex by cortical spreading depression (CSD) significantly increased the dose of desacetyl lanatoslde C required to induce A-V block and ventricular fibrillation. To examine the role of the posterior hypothalamus in the increased resistance of decorticated rats to arrhythmia induced by toxic doses of desacetyl lanatoside C, four groups of animals were injected with this drug: group 1 rats had a craniotomy; group 2 rats had a craniotomy and functional decortication; group 3 rats had a craniotomy and a hypothalamic lesion; and group 4 rats had a craniotomy, hypothalamic lesion and functional decortification. The dose of drug required to induce A-V block and ventricular fibrillation was significantly less in group 1, than in groups 2,3 and 4, and there was no statistically significant difference between these last three groups. These results are consistent with the hypothesis that the increased resistance to arrhythmia induced by desacetyl lanatoside C in decorticated rats is mediated by the posterior hypothalamus.

Production of superoxide anions in the incubation medium of hippocampal slices can induce long-term potentiation (LTP). Other reactive oxygen species (ROS) such as hydrogen peroxide are able to modulate LTP and are likely to be involved in aging mechanisms. The present study explored whether intracerebroventricular (ICV) injection of oxidant or antioxidant molecules could affect LTP in vivo. With this aim in mind, field excitatory post-synaptic potentials (fEPSPs) elicited by stimulation of the perforant pathway were recorded in the dentate gyrus of the hippocampal formation in urethane-anesthetized rats. N-acetyl-Lcysteine, hydrogen peroxide (H2O2) or hypoxanthine/xanthineoxidase solution (a superoxide producing system) were administrated by ICV injection. The control was represented by a group injected with saline ICV. Ten minutes after the injection, LTP was induced in the granule cells of the dentate gyrus by high frequency stimulation of the perforant pathway. Neither the H2O2 injection or the N-acetyl-L-cysteine injection caused any variation in the fEPSP at the 10-min post-injection time point, whereas the superoxide generating system caused a significant increase in the fEPSP. Moreover, at 60 min after tetanic stimulation, all treatments attenuated LTP compared with the control group. These results show that ICV administration of oxidant or antioxidant molecules can modulate LTP in vivo in the dentate gyrus. Particularly, a superoxide producing system can induce potentiation of the synaptic response. Interestingly, ICV injection of oxidants or antioxidants prevented a full expression of LTP compared to the saline injection.