bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablation of Pituitary Pro‐Opiomelanocortin (POMC) Cells Produces Alterations in Hypothalamic POMC mRNA Levels and Midbrain µ Opioid Receptor Binding in a Conditional Transgenic Mouse Model
Authors: Zhou Y. , Unterwald E. M. , Ho A. , LaForge K. S. , Yuferov V. P. , Kreuter J. , Sirianni M. J. , Allen R. G. , Kreek M. J. 
Published: March 2003

AbstractThe hypothalamic‐pituitary‐adrenal (HPA) axis is regulated by stress‐related excitatory inputs, and various inhibitory and negative‐feedback controls by glucocorticoids and opioids, including pro‐opiomelanocortin (POMC)‐derived peptides. The role of POMC‐derived peptides of pituitary origin in the modulation of brain POMC mRNA expression and opioid receptor binding was investigated using a line of transgenic mice that express a fusion gene composed of the pituitary expression‐specific promoter region of the POMC gene driving the herpes simplex viral‐1 thymidine kinase (TK). Male adult mice were treated with the antiherpes agent ganciclovir that selectively ablates cells expressing TK. Following treatment, POMC mRNA levels, measured by quantitative solution hybridization/RNase protection assays, were decreased by 48% in the pituitary of the TK+/+ mice, reflecting an expected loss of the pituitary corticotrope POMC cells. This treatment also significantly lowered pituitary β‐endorphin immunoreactivity content and plasma concentrations of corticosterone. In contrast, POMC mRNA levels were increased by 79% in the hypothalamus of the TK+/+ mice with pituitary POMC cell ablation. Binding of [3H]DAMGO to µ opioid receptors, as measured by quantitative autoradiography, was significantly reduced in several brain regions including the central grey, median raphe and superficial grey layer of the superior colliculus. These regions are innervated by hypothalamic POMC neurones. No significant differences in binding to either κ or δ opioid receptors were found in the brain regions studied. These results suggest that POMC‐derived peptides of pituitary origin may exert a tonic negative‐feedback effect on hypothalamic POMC neurones. In turn, the downregulation of central µ opioid receptors in this model may be mediated through a mechanism related to hypothalamic POMC overexpression.
Photorefractoriness of Immune Function in Male Siberian Hamsters (Phodopus sungorus)
Authors: Prendergast B. J. , Wynne‐Edwards K. E. , Yellon S. M. , Nelson R. J. 
Published: March 2003

AbstractShort days induce multiple changes in reproductive and immune function in Siberian hamsters. Short‐day reproductive inhibition in this species is regulated by an endogenous timing mechanism; after approximately 20 weeks in short days, neuroendocrine refractoriness to short‐day patterns of melatonin develops, triggering spontaneous recrudescence of the reproductive system. It is unknown whether analogous mechanisms control immune function, or if photoperiodic changes in immune function are masked by prevailing photoperiod. In Experiment 1, 3 weeks of exposure to long days was not sufficient to induce long‐day‐like enhancement of in vitro lymphocyte proliferation in short‐day adapted male Siberian hamsters. Experiment 2 tested the hypothesis that immunological photorefractoriness is induced by prolonged exposure to short days. Adult male hamsters were gonadectomized or sham‐gonadectomized and housed in long (14 h light/day) or short (10 h light/day) photoperiods for 12, 32 or 40 weeks. Somatic and reproductive regression occurred after 12 weeks in short days, and spontaneous recrudescence was complete after 32–40 weeks in short days, indicative of somatic and reproductive photorefractoriness. In gonad‐intact hamsters, 12 weeks of exposure to short days decreased the number of circulating granulocytes and increased the number of B‐like lymphocytes. After 32 weeks in short days, these measures were restored to long‐day values, indicative of photorefractoriness; castration eliminated these effects of photoperiod. In both intact and castrated hamsters, in vitro proliferation of splenic lymphocytes was inhibited by 12 weeks of exposure to short days. After 40 weeks in short days lymphocyte proliferation was restored to long‐day values in intact hamsters, but remained suppressed in castrated hamsters. These results suggest that short‐day‐induced inhibition of lymphocyte function does not depend on gonadal regression, but that spontaneous recrudescence of this measure is dependent on gonadal recrudescence. In Experiment 3, in vitro treatment with melatonin enhanced basal proliferation of lymphocytes from male hamsters exposed to short days for 12 weeks, but had no effect on lymphocytes of photorefractory hamsters or long‐day control hamsters. Lymphocytes of castrated hamsters were unresponsive to in vitro melatonin, suggesting that photoperiodic changes in gonadal hormone secretion may be required to activate mechanisms which permit differential responsiveness to melatonin depending on phase in the annual reproductive cycle. Together, these data indicate that, similar to the reproductive system, the immune system of male Siberian hamsters exhibits refractoriness to short days.
Leptin Uptake by Serotonergic Neurones of the Dorsal Raphe
Authors: Fernández‐Galaz M. C. , Diano S. , Horvath T. L. , Garcia‐Segura L. M. 
Published: March 2003

AbstractThe effects of leptin on food intake, metabolism, sleep patterns and reproduction may be mediated, in part, by the midbrain serotonergic systems. Here, we report on the distribution of neurones that accumulate leptin in the raphe nuclei of male and female rats after intracerebroventricular administration of mouse recombinant leptin labelled with digoxigenin. Direct leptin‐targeted cells were present in the periventricular grey, pontine and raphe nuclei. Confocal microscopy revealed that raphe neurones which accumulated leptin were predominantly serotonergic. The temporal pattern of leptin accumulation by raphe neurones showed a marked gender difference: 6 h after leptin administration, all male and female rats showed massive leptin binding in the dorsal raphe, while 30 min after leptin treatment, only 10% of male rats exhibited leptin‐labelled cells in contrast to 50% of females. The present observations reveal that leptin can be selectively accumulated by serotonergic neurones in the raphe nuclei and that this mechanism is gender specific. These findings support the idea that the midbrain serotonergic system is an important mediator of the effects of leptin on brain function and may provide an explanation for gender differences in metabolism regulation and its coordination with higher functions of the brain.
Sexual Differentiation of Astrocyte Morphology in the Developing Rat Preoptic Area
Authors: Amateau S. K. , McCarthy M. M. 
Published: March 2003

AbstractThe preoptic area is an important brain region controlling sex‐typic behaviour and physiology, and astrocytes of this region are responsive to steroids perinatally. Utilizing glial fibrillary acidic protein immunocytochemistry, the morphology of astrocytes in the preoptic area of male and female rat pups was examined on the day of birth and on postnatal day 3. As early as the day of birth, astrocytes of the male preoptic area exhibit both significantly greater primary process length and number of primary processes, and these differences remain at postnatal day 3. Application of exogenous steroid to females suggested that gonadal steroids, in particular oestradiol, mediate the sex difference. Pups received 100 µg of steroid on the day of birth and again on postnatal day 1, and astrocyte morphology was assessed on postnatal day 3. Both oestradiol and testosterone induced significant changes in process length and number compared to vehicle‐treated controls. Astrocytes of oestradiol‐treated females did not differ on PN3 from those of PN3‐untreated males. Exposure to the nonaromatizable steroid, dihydrotestosterone, had no effect on any attribute of astrocyte morphology. This suggests the effects induced by testosterone are mediated by oestradiol following local aromatization of the steroid, and not through direct activation of the androgen receptor. Astrocytes are important in synapse formation and efficacy, and we hypothesize a role for astrocyte complexity and differentiation in the establishment of synaptic patterning.
Cerebral Insulin Increases Brain Response to Glucose
Authors: Alquier T. , Leloup C. , Atef N. , Fioramonti X. , Lorsignol A. , Pénicaud L. 
Published: March 2003

AbstractThe hypothalamus participates in the regulation of carbohydrate metabolism involving a feedback loop between the brain and the periphery in which glucose‐sensitive hypothalamic areas appear to be involved. We have previously shown that a glucose injection (9 mg/kg) in the carotid artery toward the brain, in an amount that did not modify glycaemia, caused a rapid and transient increase in plasma insulin concentrations. To determine whether central insulin could influence this response, we investigated the change in central glucose‐induced insulin secretion in intracerebroventricular (i.c.v) insulin‐injected rats and in hyperinsulinaemic obese Zucker rats. Central glucose‐induced insulin secretion was increased by 50% in i.c.v. insulin‐injected rats compared to control rats. When a similar test was performed at a lower dose of glucose (3 mg/kg), a significant insulin secretion was observed only in rats submitted to a prior central insulin injection. These data indicate an increase in the brain response to glucose after insulin treatment. Using an identical lower glucose dose, we also demonstrated an enhanced brain glucose sensitivity in hyperinsulinaemic and insulin‐resistant obese Zucker rats. Together, these results indicate that acute i.c.v. insulin or pathological hyperinsulinaemic state (i.e. obese Zucker rat) modulates the nervous control of insulin secretion by increasing the brain response to glucose.
Influence of muscle contraction and jaw movement speed on the estimation of chewing force from elevator muscle EMG
Authors: PRÖSCHEL P. , RINNE H. , MORNEBURG T. 
Published: March 2003

Recent studies have shown that an additional muscle activity (AMA) in chewing was responsible for excessive masticatory forces that had been estimated from isometric bite force–activity relations. Our aim was to test the thesis that this AMA could be identical to the speed‐dependent ‘anticipatory activity’ that was found in symmetrical jaw closing (Abbink et al., 1999). In this case, forces estimated from EMG should be realistic for slow mastication, but should strongly increase with faster chewing movements.In 56 dentate volunteers the activities of bilateral masseter and anterior temporal muscles were measured during (a) right‐sided chewing, (b) right‐sided isometric clenching on a bite fork with alternating loads. These biting tasks were carried out with slow, habitual and fast contraction/movement speeds (30, 64, 102 cycles min−1). Masticatory forces were estimated for each speed by putting activities found in task (a) into bite force/activity relations obtained from task (b).In slow and habitual mastication, activities of the working side masseter were equal and exceeded the corresponding clenching activities by factors of 2·8 and 2·4, respectively (P < 0·001). Consequently, forces estimated from slow (680 N) and habitual (695 N) chewing did not differ significantly and were unrealistically high. These estimated forces and hence the corresponding AMAs did not depend on the speed movement in the same way as the anticipatory activity described inAbbink et al. (1999). In contrast, forces estimated from fast chewing (811 N) were significantly higher (P < 0·001) and corresponding AMAs qualitatively behaved like anticipatory activities. In conclusion, the AMA in chewing could be explained by anticipatory muscle activity for high movement speeds. In slow and habitual chewing however, the AMA may contain amounts of activity with a different origin.
Palatal plate of different designs for the suppression of masseter muscle activity during sleep. A challenge to the concept of placebo splint
Authors: MINAGI S. , OKAMOTO M. , SHIMAMURA M. , SATO T. 
Published: March 2003

Several designs of palatal appliance have been reported for the treatment of craniomandibular disorders. However, the effect of these appliances has not yet been fully clarified. This study aimed to reveal the effect of palatal appliances of different design on masseter muscle activity during sleep.Four volunteers (three women and one man, mean age 36·0 years) were used in this study. For each subject, four different types of palatal appliances were used. The palatal appliances were (1) horse shoe type (1 mm thick), (2) thin appliance which covered the whole palate (1 mm thick), (3) thick appliance which filled the palatal concavity and (4) appliance with half the thickness of the third appliance.These appliances were worn for 1 week in a randomized sequence with 1‐week interval between each appliance. Right masseter muscle EMG was recorded three nights per week at home. The EMG signal longer than 0·25 s was classified as a burst and a signal shorter than 0·25 s was classified as a brief burst of fragmentary myoclonus (FM).Mean number of burst per hour for four subjects were 7·99 ± 7·32, 3·52 ± 1·95, 5·90 ± 3·99, 2·87 ± 2·87 and 9·96 ± 6·02 for base line, appliance 1, 2, 3 and 4, respectively. Mean number of FM per hour were 136·86 ± 69·88, 90·53 ± 41·19, 99·49 ± 39·29, 71·66 ± 24·66 and 144·39 ± 42·97, respectively. From these results, it was suggested that the thick palatal appliance suppressed the masseter muscle activity during sleep most effectively. Also, the results for appliance 4 questioned the concept of placebo effect for non‐occlusal appliances.
Eastward long distance flights, sleep and wake patterns in air crews in connection with a two‐day layover
Authors: LOWDEN ARNE , ÅKERSTEDT TORBJÖRN 
Published: March 2003

SummaryThe present study describes the spontaneous sleep/wake pattern in connection with an eastward (Stockholm to Tokyo,+8 h) transmeridian flight and short (51 h) layovers. To describe all sleep episodes and the recovery process across 4 days, and to relate adjustment to individual differences, 49 Scandinavian Airlines System (SAS) air crew were monitored for 9 days with activity monitors and sleep/wake diary before‐during‐after flight. The outbound flight involved a period of wakefulness extended to 21 h, frequently (87% of air crew) terminated by a long nap in Tokyo which was calm but difficult to wake up from. Then followed two night oriented sleep periods of normal length but of reduced efficiency, containing many and long awakenings. Napping was common during the extended periods of wakefulness, particularly during flights. During the recovery days, ease of rising from sleep in the mornings was difficult throughout, and feelings of not being refreshed returned to baseline levels on the third recovery sleep. Elevated daytime sleepiness (24% of the day) was observed on the first recovery day. No individual differences related to gender, age or position (cabin/pilot) was found in sleep strategy. Poor adjusters, subjects with a perceived lowered capacity on recovery days, showed more premature awakenings abroad and less refreshing sleep during the last 12 months, suggesting a decreased ability to cope with air crew scheduling. Comparisons with a westbound flight showed the eastbound flight layover sleep to be more problematic and containing more napping.
Sleep organization in the first year of life: Developmental trends in the quiet sleep–paradoxical sleep cycle
Authors: Ficca G. , Fagioli I. , Salzarulo P. 
Published: March 2003

SUMMARYThe night sleep of 48 healthy drug‐free infants, aged 1–54 weeks, was recorded and analysed in order to show how cycles contribute to sleep episode organization and how the balance among different sleep states (i.e. quiet sleep, paradoxical sleep and ambiguous sleep) within cycles changes as a function of age.A greater proportion of time spent in cycles (TCT) on total sleep time (TST), as a result of the lengthening of sleep cycles, was found in older infants, whereas sleep out of cycles decreases with age. The internal structure of the sleep cycles also changes with age, because of the increase in the proportion of quiet sleep (QS), the appearance of slow wave sleep (SWS) from the 21st week onwards, and the decrease in ambiguous sleep. The proportion of paradoxical sleep (PS), however, remains stable throughout the first year of age.The improvement of sleep organization across the first year of life is paralleled by an internal restructuring of the cycle, involving mainly changes in QS. We may speculate that both changes, one involving the lengthening of cycle and the other involving the increase in QS component, contribute to the improvement of biological and psychological sleep functions during development.
Prenatal protein malnourished rats show changes in sleep/wake behavior as adults
Authors: Datta Subimal , Patterson Elissa H. , Vincitore Michele , Tonkiss John , Morgane Peter J. , Galler Janina R. 
Published: March 2003

SUMMARYPrenatal protein malnutrition significantly elevates brain levels of serotonin in rats, and these levels remain elevated throughout their lives. This biogenic amine is involved in the regulation of many physiological functions, including the normal sleep/wake cycle. The present study examined the effects of prenatal protein malnutrition on the sleep/wake cycle of freely moving adult rats. Six prenatally protein malnourished (6% casein) and 10 well‐nourished (25% casein) male rats (90–120‐day‐old) were chronically implanted with a standard set of electrodes (to record cortical electroencephalogram, neck muscle electromyogram, electrooculogram, and hippocampal theta wave) to objectively measure states of sleep and wakefulness. Six‐hour polygraphic recordings were made between 10.00 and 16.00 h; a time when the rats normally sleep. Prenatally malnourished rats spent 20% more time in slow wave sleep (SWS) compared to the well‐nourished rats. The total percentage of time spent in rapid eye movement (REM) sleep was 61% less in prenatally malnourished rats compared to well‐nourished control rats. These findings demonstrate the adverse consequences of prenatal protein malnutrition on the quality and quantity of adult sleep in rats. These sleep changes are potentially detrimental to normal social behavior and cognitive functions. Prenatally malnourished rats are an excellent animal model to study the role of endogenous serotonin in the regulation of the normal sleep/wake cycle.
Regional cerebral blood flow during light sleep – a H215O‐PET study
Authors: Kjaer Troels W. , Law Ian , Wiltschiøtz Gordon , Paulson Olaf B. , Madsen Peter L. 
Published: March 2003

SummaryThis is the first report on the distribution of regional cerebral blood flow (rCBF) changes during stage‐1 sleep or somnolence. Two hypotheses were tested: (A) that rCBF differed between the awake relaxed state and stage‐1 sleep, (B) that hypnagogic hallucinations frequently experienced at sleep onset would be accompanied by measurable changes in rCBF using positron emission tomography (PET). Eight subjects were PET‐scanned with 15O‐labeled water injection in three conditions: awake, stage‐1 sleep with reportable experiences and stage‐1 sleep without reportable experiences. Electroencephalography (EEG) was performed continuously during the experiment. Sleep interviews were performed after each scan. The EEG was scored blindly to determine sleep stage. The sleep interviews revealed a substantial increase in how unrealistic and how leaping the thoughts were during stage‐1 sleep. During sleep there was a relative flow increase in the occipital lobes and a relative flow decrease in the bilateral cerebellum, the bilateral posterior parietal cortex, the right premotor cortex and the left thalamus. Hypnagogic experiences seemed not to be associated with any relative flow changes. The topography of the occipital activation during stage‐1 sleep supports a hypothesis of this state being a state of imagery. The rCBF decreases in premotor cortex, thalamus and cerebellum could be indicative of a general decline in preparedness for goal directed action during stage‐1 sleep. Stage‐1 sleep seems more similar to other forms of altered awareness, for example, relaxation meditation than to deeper sleep stages. We are of the opinion that stage‐1 sleep represents the dreaming state of wakefulness, while rapid eye movement (REM) sleep reflects the dreaming state of the unaware, sleeping brain.
Combined index of heart rate variability and oximetry in screening for the sleep apnoea/hypopnoea syndrome
Authors: Raymond Ben , Cayton R. M , Chappell M. J. 
Published: March 2003

SUMMARYMany sleep centres employ a preliminary screening test in order to reduce the number of polysomnographies required in the routine diagnosis of the sleep apnoea/hypopnoea syndrome (SAHS). We investigated the combination of heart rate and oximetry information as a means of performing this test. A retrospective study of 100 patients with suspected SAHS was made. All patients had in‐hospital polysomnography on one night. We estimated the number of respiratory event‐related arousals by counting the number of autonomic arousals (assessed on the basis of changes in the heart interbeat interval) that were coincident with a rise in oximetry. The hourly index of such events was denoted the ‘cardiac‐oximetry disturbance index’ (CODI). The median apnoea/hypopnoea index (AHI) was 16.5 (range 1.0–93.6) h−1. The CODI correlated significantly with the AHI (Spearman correlation coefficient rs = 0.88, P < 0.01), and the area (± standard error) under the receiver operating characteristic (ROC) was 0.94 ± 0.05. Oximetry alone (based on 4% dips) was a less effective screening test (rs = 0.80, P < 0.01; area under ROC 0.83 ± 0.06). Using 2% dips in oximetry offered comparable performance with the CODI (rs = 0.91, P < 0.01; area under ROC 0.93 ± 0.04). The CODI was better correlated with the electroencephalograph arousal index (rs = 0.84, P < 0.01) than was oximetry (2% dips, rs = 0.57, P < 0.01). The CODI algorithm also offers an informal measure of self‐validation: a large discrepancy between the number of autonomic arousals and the number of rises in oximetry indicates the presence of autonomic arousals without changes in oximetry (or vice versa). This self‐validation mechanism identified several patients in this study, and may be useful in identifying sleep disruption due to chronic pain or other causes.