Biomedical subjects

F Obál

Publications and source records attributed to F Obál.

At least 19 recordsLinked to original sources

PubMed1998

Albumin enhances sleep in the young rat.

Rats 4 to 7 days after weaning received intraperitoneal (i.p.) injections of vehicle (baseline day), and either serum (2 mL of lyophilized rabbit serum), 140 mg of rat albumin, or hyperosmotic NaCl (experimental day). Injections were given 1 h before light onset. Sleep-wake activity and cortical brain temperature were recorded during the subsequent 12-h light period. The intensity of non-rapid eye movement sleep (NREMS) was characterized by the power density values of the electroencephalogram slow-wave activity. The sera and albumin preparations enhanced both NREMS and slow-wave activity for 5 to 6 h starting during Hour 2 after light onset. Rapid eye movement sleep (REMS) tended to decrease. Modest (0.6 degrees C maximum deviation) biphasic changes were observed in cortical brain temperature with initial decreases for 3 h followed by rises between Hours 3 and 9 of the light period. There were no differences in the sleep responses to albumin between male and female rats. Albumin also enhanced NREMS in young rats on a protein-rich diet. A significant negative correlation was found between the NREMS promoting activity of albumin injections and the body weight of the rats. NaCl solution with the same osmolarity as that of the albumin solution failed to alter sleep. I.p. albumin injection elicited significant increases in the concentrations of cholecystokinin-like immunoreactivity in the plasma. Sleep-promoting materials (hormones) in the albumin fraction, the calorigenic or nutritional value of proteins, the release of somnogenic cytokines by albumin, or endogenous humoral mechanisms stimulated by proteins (e.g., cholecystokinin or the somatotropic axis) might mediate the enhanced sleep after albumin.

Albumins↗

PubMed1998

Sleep-associated changes in interleukin-1beta mRNA in the brain.

Much evidence implicates interleukin-1beta (IL-1beta) in sleep regulation. Two previous studies indicated that levels of IL-1beta in mRNA were affected by sleep. In the current study, levels of IL-1beta mRNA and IL-1 receptor assessory protein (IL-1RAP) mRNA were determined 1 h after the beginning of light and dark periods and after sleep deprivation, using the reverse transcriptase-polymerase chain reaction (RT-PCR) and mutated internal standards. Daytime samples contained relatively more IL-1beta mRNA than nighttime samples, and levels of IL-1beta mRNA were higher after sleep deprivation. These changes occurred in the hypothalamus, hippocampus, cerebral cortex, and mesencephalon/pons. In contrast, the IL-1 RAP mRNA level did not seem to be affected by sleep.

Animals↗

PubMed1998

Sleep deprivation increases rat hypothalamic growth hormone-releasing hormone mRNA.

Much evidence indicates that growth hormone-releasing hormone (GHRH) is involved in sleep regulation. We hypothesized that GHRH mRNA would increase and somatostatin (SRIH) mRNA would decrease during sleep deprivation. With the use of RT-PCR and truncated internal standards, rat hypothalamic GHRH mRNA and SRIH mRNA levels were evaluated after sleep deprivation. After 8 or 12 h of sleep deprivation there was a significant increase in rat hypothalamic GHRH mRNA expression compared with time-matched control samples. Hypothalamic GHRH mRNA levels were not significantly different from control values after 1 or 2 h of recovery after 8 h of sleep deprivation or after 2 h of recovery after 12 h of sleep deprivation. In control animals, variations in hypothalamic GHRH mRNA levels were observed. GHRH mRNA expression was significantly higher in the afternoon than at dark onset or during the dark period. SRIH mRNA levels were significantly suppressed at the termination of an 8-h sleep deprivation period and were significantly higher after dark onset than in the morning. The alterations in GHRH and SRIH mRNA expressions after sleep deprivation and recovery support the notion that GHRH plays an important role in sleep homeostasis and suggest that these neuropeptides may interact reciprocally in modulating sleep as they do in the control of growth hormone secretion.

Animals↗

PubMed1997

Sleep in rats rendered chronically hyperprolactinemic with anterior pituitary grafts.

A hyperprolactinemic rat model [rats bearing anterior pituitary grafts under the capsule of the kidney (AP-grafted rats)] was used to study sleep-wake activity and cortical brain temperature (T(crt)). Fisher 344 male rats (n = 24) were implanted with anterior pituitaries from rat pups; the control rats (n = 12) were sham-operated. Sleep-wake activity and T(crt) were recorded for 2 days between weeks 3 and 7 after surgery. The hyperprolactinemic state of the rats was confirmed by plasma prolactin (PRL) assays on week 7 and by determination of PRL mRNA levels in the anterior pituitary of the AP-grafted rats. Neither growth hormone plasma concentration nor pituitary mRNA levels were affected by the pituitary grafts. Duration of non-rapid eye movement sleep (NREMS) was slightly enhanced in the AP-grafted rats. A large increase in rapid eye movement sleep (REMS) during the 12-h light period was the major effect of the implantation of the extra pituitaries. Both the duration and the frequency of the REMS episodes increased and persisted for weeks 4-7 post-implantation. The nocturnal states of vigilance, T(crt), and intensity of NREMS (EEG slow wave activity) were not altered. The results clearly indicate that the enhancements in REMS persist during hyperprolactinemia, and support the hypothesis that PRL possesses REMS-promoting activity.

Analysis of Variance↗

PubMed1997

Diurnal variations of interleukin-1 beta mRNA and beta-actin mRNA in rat brain.

Interleukin-1 beta (IL-1 beta) is posited to play an important physiological role in brain functions in addition to its better defined role in pathology. The experiments described herein were performed to determine if IL-1 beta mRNA and beta-actin display diurnal rhythms in various areas of brain. Rats were sacrificed at 4 h intervals across a 12:12 h light/dark cycle. Hypothalamic, hippocampal and cortical IL-1 beta mRNA peaked just after lights were turned on, declined slightly during the remaining light period and stayed low in the dark. There were no significant changes in IL-1 beta mRNA in brain stem or cerebellum samples. beta-actin mRNA levels were relatively constant across the day in the hypothalamus, brain stem and cerebellum. However, beta-actin mRNA levels were lower during the day than during the night in the hippocampus and cortex.

Actins↗

PubMed1997

Changes in rat sleep after single and repeated injections of the long-acting somatostatin analog octreotide.

Somnogenic activity is attributed to both growth hormone (GH) and GH-releasing hormone (GHRH). The aim of our experiments was to study sleep after suppression of the somatotropic axis by means of administration of a long-lasting somatostatin analog, octreotide. Rats received subcutaneous injections of physiological saline (baseline), octreotide (1, 10, and 200 microg/kg), or a control solution just before light onset, and sleep-wake activity and cortical brain temperature were recorded for 23 h. Each dose of octreotide slightly promoted rapid eye movement sleep (REMS) during the 12-h light period. Non-REM sleep (NREMS) was strongly suppressed for 1 h in response to 10 and 200 microg/kg octreotide. This was followed by slight increases in NREMS time and significant enhancements in electroencephalogram slow-wave activity during NREMS after 200 microg/kg octreotide. The octreotide-induced inhibition of the somatotropic axis, as determined by plasma GH levels, vanished by the time sleep increased. Another group of rats received 10 microg/kg octreotide twice a day for 5 days. This treatment elicited persistent decreases in both NREMS time and NREMS intensity. The results support the previously reported REMS-promoting activity of somatostatin in rats. The decreases in sleep after repeated injections of octreotide are attributed to a withdrawal of the normal sleep-promoting activity of GH. The role of GHRH-GH in octreotide-induced acute suppression of NREMS is currently not clear. Other mechanisms, such as mimicking central transmitter functions of somatostatin by octreotide, should also be considered.

Animals↗

PubMed1997

Antiserum to growth hormone decreases sleep in the rat.

To determine whether an acute withdrawal of growth hormone (GH) alters sleep, the effects of antiserum to GH (GH-AS) on sleep were studied in the rat. Sleep-wake activity and cortical brain temperature (Tc) were recorded for 2 days after systemic injection of physiological saline. Then, one group of rats (n = 6) received GH-AS whereas another group of rats was injected with normal rabbit serum (n = 6). The injections were given 1 h before light onset, and the rats' behaviors were recorded for 23 h during the subsequent 12-hour light and 12-hour dark period. Sleep and Tc were not altered after normal rabbit serum. The durations of both rapid eye movement sleep (REMS) and non-REMS (NREMS), and the EEG slow-wave activity during NREMS were significantly suppressed during the light period following the injection of GH-AS. Tc tended to decrease for 3 h and a small rise was observed thereafter during the light period, but these changes were not statistically significant. The assay of GH in plasma samples obtained at 30-min intervals for 5 h after injection of normal rabbit serum or GH-AS verified the decreases in plasma GH concentrations in response to GH-AS. It is suggested that GH may promote sleep possibly via some metabolic actions.

Animals↗

PubMed1996

Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency in the somatotropic system.

Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)-GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine hydroxylase flanking sequence, targeting the production of hGH to sites of tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates. Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the light and the dark period in the transgenic mice; rapid eye movement sleep (REMS) was not altered. The results provide evidence that the somatotropic axis contributes to normal sleep regulation.

Animals↗

PubMed1996

The effects of immunolesions of nerve growth factor-receptive neurons by 192 IgG-saporin on sleep.

Low-affinity nerve growth factor (NGF) receptors are present on the cholinergic neurons of the basal forebrain. We studied the effects of 192 IgG-saporin, a specific immunotoxin for the NGF receptor-positive, cholinergic basal forebrain neurons, on sleep, the power spectrum of the electroencephalogram (EEG), and body temperature. After 3 d baseline recordings, 12 male rats were injected intracerebroventricularly with 4 micrograms 192 IgG-saporin. EEG, motor activity, and brain temperature were recorded for 23 h on the first, third, fifth, and seventh day after the treatment. 192 IgG-saporin did not affect the total daily amounts but altered the circadian distribution of sleep. On days 1 and 3 after the injection of the immunotoxin, the amount of non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) increased during the dark period, whereas during the light both NREMS and REMS decreased. On day 5, these changes were less pronounced and sleep completely returned to the baseline by day 7. The EEG was suppressed in each frequency band and each vigilance state, and, in contrast to sleep, these changes in EEG persisted for 7 days. Brain temperature was decreased from day 3. These results suggest that NGF receptor-positive, cholinergic basal forebrain neurons are not necessary for the maintenance of total sleep time but contribute to the generation of normal EEG and the maintenance of brain temperature.

Analysis of Variance↗

PubMed1996

Effects of systemic GHRH on sleep in intact and hypophysectomized rats.

The role of pituitary growth hormone (GH) in the mediation of enhanced sleep elicited by GH-releasing hormone (GHRH) was studied in the rat. Intact and hypophysectomized (HYPOX) rats received systemic injections of GHRH or physiological saline. GHRH (0.5, 5.0, or 50 micrograms/kg in the intact rats and 0.5 or 50 micrograms/kg in HYPOX rats) was injected 6 h after light onset (P.M. injection) or just before light onset (A.M. injection, 0.5 microgram/kg in both A.M. groups). Sleep-wake activity and brain cortical temperature were recorded for 23 h (12 h light + 11 h dark). A.M. injection of GHRH did not alter sleep in normal or HYPOX rats. Each dose of P.M. GHRH increased rapid-eye-movement sleep (REMS) during 6 h postinjection in the intact rats. Hypophysectomy abolished the REMS-promoting activity of GHRH. P.M. injection of 0.5 microgram/kg GHRH increased non-REM sleep (NREMS) and enhanced electroencephalogram slow-wave activity during NREMS in both the intact and the HYPOX rats. The NREMS-promoting activity disappeared when the dose of GHRH was increased in the intact rats, whereas a tendency to enhanced NREMS was still observed after 50 micrograms/kg GHRH in the HYPOX rats. GHRH stimulated GH secretion dose dependently in the intact rats. A.M. injection of 0.5 microgram/kg GHRH tended to be less effective in stimulating GH release than the same dose administered P.M. The results confirm the time-of-day variations in the GHRH effects on sleep previously reported in human subjects. It is likely that pituitary GH is involved in the mediation of the REMS-promoting activity of GHRH but not in the NREMS-promoting activity of GHRH. Nevertheless, the results do not exclude the possibility that GH may modulate NREMS.

Animals↗

PubMed1995

Promotion of sleep by heat in young rats.

The aim of the experiments was to study the effects of a moderate heat load on sleep in young (26-day-old) rats and to determine whether the sleep-promoting effect of heat results from stimulation of the homeostatic sleep process. The changes in sleep-wake activity, electroencephalogram slow wave activity (SWA) during non-rapid eye movement sleep (NREMS) and cortical temperature (Tcrt) were determined during and after long (24-h) and short (2.5-h) heat loads (elevation of ambient temperature from 26 degrees C to 32 degrees C), and after total sleep deprivation (SD) combined with a short-term heat load. The heat exposures elicited increases in Tcrt and rectal temperature (2 and 1.7 degrees C respectively). The long-term heat load induced persistent, albeit slight enhancements in NREMS. Rapid eye movement sleep (REMS) increased with a 12-h delay during the 24-h heat load. Heat elicited an immediate large increase in SWA. After this initial increase, SWA declined and tended to fall below the baseline level during the last 12 h of the 24-h heat load. SWA and REMS were significantly suppressed after termination of 24-h heat loading. The increased SWA during the short-term heat load was not followed by subsequent alterations in sleep when the ambient temperature had returned to normal. However, after the combination of SD with the short-term heat load the durations of NREMS and SWA were significantly enhanced compared with those found after SD at 26 degrees C. The results are interpreted as suggesting that heat increases NREMS in the young rat by the same mechanism as is involved in the enhancement of NREMS after SD: a stimulation of sleep drive.

Animals↗

PubMed1995

Growth-hormone-releasing hormone mediates the sleep-promoting activity of interleukin-1 in rats.

The involvement of endogenous growth-hormone-releasing hormone (GHRH) in the sleep-promoting activity of interleukin-1 (IL1) was studied. The effects on sleep of intracerebroventricular injection of IL1 were tested in rats pretreated with intracerebroventricular antibodies to GHRH (GHRH-ab). One group of rats received two treatments each consisting of two injections, control IgG + physiological saline (IgG + Sal) and on another day GHRH-ab + Sal, whereas another group of rats received IgG + Sal, IgG + IL1 and GHRH-ab + IL1 on separate days with one day off between the various treatments. IgG or GHRH-ab was injected 6 h prior to dark onset; Sal or IL1 was administered at dark onset. Recording of sleep-wake activity and cortical brain temperature (Tcrt) was started with the injection of IgG or GHRH-ab and continued for 18 h. GHRH-ab (GHRH-ab + Sal) suppressed rapid eye movement sleep (REMS), non-REMS (NREMS) and EEG slow-wave activity (SWA) during NREMS throughout the recording period. IL1 treatment (IgG + IL1) enhanced NREMS and SWA, and induced fever for 6 h. Pretreatment with GHRH-ab (GHRH-ab + IL1) abolished the IL1-induced increases in NREMS, attenuated the enhancements in SWA, and suppressed fever for 6 hours after IL1. The results indicate that the sleep-promoting activity of IL1 is mediated at least in part via GHRH. The suppression of the IL1-induced fever by GHRH-ab might be attributed to an inhibition of hypothalamic somatostatin.

Animals↗

PubMed1995

Prolactin and rapid eye movement sleep regulation.

During the past few years data have accumulated suggesting the involvement of prolactin (PRL) in rapid eye movement sleep (REMS) regulation. Pituitary PRL secretion seems to be, at least in part, sleep-dependent. PRL is also found in the central nervous system. PRL-containing neurons in the hypothalamus project to various structures in the brain. Systemic injection of PRL promotes REMS in rats, cats and rabbits. Intracerebroventricular injection of PRL enhances REMS in rats. Stimulation of endogenous PRL secretion by vasoactive intestinal peptide (VIP) also promotes REMS. Immunoneutralization of blood-borne PRL slightly reduces REMS. Various observations (hypoprolactinemic and hyperprolactinemic rats) indicate that PRL may act on REMS via modulating the diurnal rhythms of REMS. It is likely that hypothalamic PRL is more important for sleep regulation than circulating PRL. Hypothalamic PRL is likely involved in the mediation of the REMS-promoting activity of VIP. We conclude that PRL has a role in REMS regulation.

Animals↗

PubMed1994

Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP.

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with beta-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.

Animals↗

PubMed1994

Sleep-associated variations in plasma renin activity and blood pressure in the rat.

Plasma renin activity (PRA) was determined in plasma samples obtained approximately at 6-min intervals during consecutive non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) periods in rats chronically implanted with EEG electrodes, a brain thermistor, and an intracardiac catheter. PRA was low in REMS and high in NREMS: this difference was statistically significant. The PRAs in wakefulness and NREMS were not different. Sleep-associated variations in systemic blood pressure (BP) were also recorded in a group of rats implanted with a chronic aortic catheter. During REMS, large oscillations superimposed on a tonic rise in BP were observed, and the end of REMS was followed by an abrupt fall in BP. This is the first demonstration of sleep-associated variations in PRA in a species other than man. The changes in BP in the rat during REMS confirm previous reports and, unlike those in many other species, are similar to those previously described in humans. The rat therefore provides a model for study of the mechanisms of the sleep-related variations in PRA and BP. The changes in PRA may reflect a regulatory response to variations in BP or may result from central mechanisms, e.g. the sleep-associated changes in serotonergic activity.

Animals↗

PubMed1994

Involvement of prolactin in the REM sleep-promoting activity of systemic vasoactive intestinal peptide (VIP).

The involvement of pituitary prolactin (PRL) in systemic vasoactive intestinal peptide (VIP)-induced sleep was studied. Male rats were implanted with electrodes for EEG-recording, with brain thermistors to record cortical temperature (Tcrt) and with chronic intracardial catheters to obtain blood samples and to deliver substances. One group of rats (n = 8) received normal rabbit serum (NS)+physiological saline (SAL) on the baseline day and was injected with NS+VIP on the experimental day. In the other group of rats (n = 6), the baseline day was followed by administration of PRL-antiserum (PRL-AS) + VIP on the experimental day. The sera and VIP or SAL were injected 30 min before and at light onset, respectively. Sleep-wake activity was then recorded for the next 12-h light period. Systemic VIP-stimulated PRL secretion as measured by RIA in serial samples obtained hour 1 postinjection. VIP also elicited selective increases in REM sleep (REMS) in the rats pretreated with NS. Tcrt was not affected by VIP. Administration of PRL-AS blocked the increase in circulating levels of free (non-IgG-bound) PRL and prevented VIP-enhanced REMS. Comparisons of the sleep effects of PRL-AS+VIP with the previously reported changes in sleep after PRL-AS alone indicate that PRL has a major role in the mediation of the REMS-promoting activity of systemic VIP. The results suggest that an increased release of endogenous pituitary PRL modulates REMS.

Animals↗

PubMed1994

[Functional study of the regeneration of nerve fibers after keratinocyte transplantation].

The functional regeneration of sensory nerves was investigated in 5 patients with skin defects (caused by leg ulcers, a burn or fasciitis necrotisans) after transplantation with a keratinocyte suspension. In this area, first the pain sense and soon after wards the cold and heat sense returned, followed finally by the flare reaction caused by the mustard oil test. No sweat production could be observed during the study, because sweat glands were not found after the keratinocyte transplantation. The reinnervation course is roughly the same for skin defects covered with split skin graft or with a keratinocyte suspension.

Adult↗

PubMed1994

Somnogenic activity of muramyl peptide-derived immune adjuvants.

Muramyl peptides (MPs) possess immunostimulatory, pyrogenic and somnogenic activities. The structural requirements of MPs for each of these activities are different though certain MPs, e.g. muramyl dipeptide (NAM-L-ala-D-isogln) possess all three activities. Several MPs are proposed for use as immune adjuvants; somnogenic and pyrogenic activities would be considered adverse side effects of such compounds. We report here that some of the putative adjuvants, GIF101, WG209 and MDP-threonine lack somnogenic and pyrogenic activities. Current results also expand our understanding of the structural requirements for these activities. Major findings are that the addition of the dipeptide L-ala-D-isogln to NAG-NAM-L-ala-D-isogln blocks the activity of the latter compound and that the amino sugar moiety of MPs, NAM, is unnecessary for somnogenic and pyrogenic activity.

Acetylmuramyl-Alanyl-Isoglutamine↗