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Biomedical subjects

F Obál

Publications and source records attributed to F Obál.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Hypothalamic releasing hormones mediating the effects of interleukin-1 on sleep.

There is a substantial literature describing the interactions between the endocrine and immune systems. Although such interactions are less well known within the brain, one major brain function altered during inflammation and infection and by several endocrine hormones is sleep. Pathological disturbances, be they inflammation, infectious disease, and/or sleep deprivation, result in altered hypothalamus-pituitary function and cytokine metabolism. In respect to hormone secretion from the pituitary, cytokines are now recognized to play an important role in modulating the neuroendocrine system. Changes in sleep provide a useful illustration of the interactions between cytokines and the hypothalamus-pituitary axis. Evidence linking interleukin-1 (IL-1) to growth hormone releasing hormone and to corticotropin releasing hormone in regard to their effects on sleep is reviewed.

Animals↗
PubMed1993

Growth hormone-releasing hormone and interleukin-1 in sleep regulation.

Growth hormone-releasing hormone (GHRH) and interleukin-1 (IL-1) are putative endogenous sleep-promoting substances. Evidence is reviewed showing that, 1) GHRH and IL-1 promote non-rapid eye movement sleep (NREMS); 2) if their production is enhanced, sleep is enhanced; and 3) if they are inhibited using either specific antibodies or peptide antagonists, sleep is reduced. Both are in the brain and both are also indirectly linked to sleep/wake cycles by various other evidence, e.g., growth hormone release and IL-1 plasma levels vary in phase with sleep/wake cycles. Finally, their actions are directly linked to each other; e.g., IL-1-induced growth hormone release is mediated via GHRH. The evidence reviewed strongly implicates both GHRH and IL-1 as key components in humoral sleep regulation. Humoral theories of sleep regulation are complementary to neural theories; both mechanisms affect each other and undoubtedly continuously interact to regulate sleep/wake cycles.

Animals↗
PubMed1993

A neuronal group theory of sleep function.

A new theory of sleep function is presented within the context of the neuronal group selection hypothesis, which emphasizes that neuronal groups compete for neurons via use-dependent synaptic formation and atrophy. It is hypothesized that sleep serves to stabilize these competitive processes by providing a pattern of stimulation that serves to maintain a synaptic infrastructure upon which wakefulness-driven synaptic changes are superimposed. Sleep is 'quantal' in nature in that sleep is a statistical property of a population of neuronal groups in different states. The theory unifies past theories of sleep function yet simultaneously provides a fundamental new paradigm for sleep research.

Journal Article↗
PubMed1992

Prostaglandins E2 and D2 have little effect on rabbit sleep.

Prostaglandins (PGs) are hypothesized to be involved in sleep regulation; PGE2 and PGD2 are major PGs in the hypothalamus of many species and are proposed to reciprocally promote wakefulness and sleep respectively. PGD2 and PGE2 are also major PGs in rabbit cerebrospinal fluid, yet their effects on rabbit sleep have not heretofore been systematically investigated. We report here that a bolus injection of PGE2 into a lateral cerebral ventricle induces dose-dependent fevers and transient sleep responses in rabbits. PGE2 induces a suppression of sleep of 24 min duration. In contrast, PGD2, across a wide range of doses (0.25-500 nmol) failed to alter sleep; however, at the highest dose it induced fever. We conclude that if PGs are involved in sleep regulation, a chronic stimulation of their production by other sleep factors is necessary.

Animals↗
PubMed1992

Antiserum to prolactin decreases rapid eye movement sleep (REM sleep) in the male rat.

Previous reports suggest that blood-born prolactin (PRL) may selectively promote rapid eye movement sleep (REMS). To study the possible involvement of endogenous PRL in sleep regulation, rats were systemically injected with either antiserum to PRL or normal rabbit serum, and the sleep-wake activity was determined during the subsequent 12-h light cycle. The administration of normal rabbit serum in physiological saline did not alter sleep-wake activity compared to control recordings, whereas the PRL antiserum caused a modest and selective suppression in REMS. Immunoreactive PRL was eliminated from the serial plasma samples obtained between 6 to 11 h after the injection of the antiserum. Brain temperature was not affected by the antiserum. The results indicate that physiological pituitary PRL secretion has a slight REMS-promoting activity in the male rat. It is speculated that an increased release of pituitary PRL or the PRL-like substance previously demonstrated in the brain may significantly stimulate REMS.

Animals↗
PubMed1992

Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation.

Previous reports suggest that the hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep, especially non-rapid-eye-movement sleep (NREMS). To evaluate the role of endogenous GHRH in sleep regulation, the effects of antibodies to rat GHRH (GHRH-ab) were studied on normal sleep, brain temperature (Tbr), and GH secretion in experiment I and on enhanced sleep after sleep deprivation in experiment II. In experiment I, affinity-purified GHRH-ab (50 and 200 micrograms) raised in goats and a control goat immunoglobulin G (IgG) preparation were injected intracerebroventricularly (icv) in rats 1 h before the onset of the light cycle, and sleep-wake activity and Tbr were recorded for the next 12 or 23 h. Both doses of GHRH-ab suppressed NREMS and REMS throughout the light cycle. Sleep durations at night were normal. Electroencephalographic (EEG) slow-wave activity, characterized by EEG slow-wave amplitudes, was reduced after GHRH-ab during both the light and the dark cycles. Plasma GH concentrations measured 6-12 h after injection of GHRH-ab (200 micrograms) were diminished. Both the control IgG and GHRH-ab elicited fever. In experiment II, the sleep-wake activity and Tbr of rats were recorded for 24 h in three experimental conditions: base-line with icv injection of IgG, 3-h sleep deprivation with icv IgG injection, and 3-h sleep deprivation with icv GHRH-ab (200 micrograms). After sleep deprivation (+IgG), a prompt increase in EEG slow-wave activity (power density analysis) and late increases in NREMS and REMS durations were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗