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1.
Int Rev Neurobiol ; 131: 207-225, 2016.
Article in English | MEDLINE | ID: mdl-27793219

ABSTRACT

Sleep is profoundly altered during the course of infectious diseases. The typical response to infection includes an initial increase in nonrapid eye movement sleep (NREMS) followed by an inhibition in NREMS. REMS is inhibited during infections. Bacterial cell wall components, such as peptidoglycan and lipopolysaccharide, macrophage digests of these components, such as muramyl peptides, and viral products, such as viral double-stranded RNA, trigger sleep responses. They do so via pathogen-associated molecular pattern recognition receptors that, in turn, enhance cytokine production. Altered sleep and associated sleep-facilitated fever responses are likely adaptive responses to infection. Normal sleep in physiological conditions may also be influenced by gut microbes because the microbiota is affected by circadian rhythms, stressors, diet, and exercise. Furthermore, sleep loss enhances translocation of viable bacteria from the intestine, which provides another means by which sleep-microbe interactions impact neurobiology.


Subject(s)
Gastrointestinal Microbiome/physiology , Sleep Wake Disorders , Sleep/physiology , Animals , Cytokines/metabolism , Humans , Sleep Wake Disorders/etiology , Sleep Wake Disorders/microbiology , Sleep Wake Disorders/pathology
2.
Neuroscience ; 156(1): 71-80, 2008 Sep 22.
Article in English | MEDLINE | ID: mdl-18694809

ABSTRACT

Cortical surface evoked potentials (SEPs) are larger during sleep and characterize a sleep-like state in cortical columns. Since tumor necrosis factor alpha (TNF) may be involved in sleep regulation and is produced as a consequence of waking activity, we tested the hypothesis that direct application of TNF to the cortex will induce a sleep-like state within cortical columns and enhance SEP amplitudes. We found that microinjection of TNF onto the surface of the rat somatosensory cortex enhanced whisker stimulation-induced SEP amplitude relative to a control heat-inactivated TNF microinjection. We also determined if whisker stimulation enhanced endogenous TNF expression. TNF immunoreactivity (IR) was visualized after 2 h of deflection of a single whisker on each side. The number of TNF-IR cells increased in layers II-IV of the activated somatosensory barrel column. In two separate studies, unilateral deflection of multiple whiskers for 2 h increased the number of TNF-IR cells in layers II-V in columns that also exhibited enhanced cellular ongogene (Fos-IR). TNF-IR also colocalized with NeuN-IR suggesting that TNF expression was in neurons. Collectively these data are consistent with the hypotheses that TNF is produced in response to neural activity and in turn enhances the probability of a local sleep-like state as determined by increases in SEP amplitudes.


Subject(s)
Evoked Potentials, Somatosensory/physiology , Sleep/physiology , Somatosensory Cortex/physiology , Tumor Necrosis Factor-alpha/physiology , Afferent Pathways/drug effects , Afferent Pathways/physiology , Animals , Cell Count , Evoked Potentials, Somatosensory/drug effects , Immunohistochemistry , Male , Nerve Tissue Proteins/biosynthesis , Neurons/drug effects , Neurons/physiology , Physical Stimulation , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-Dawley , Sleep/drug effects , Somatosensory Cortex/drug effects , Touch/physiology , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/pharmacology , Up-Regulation/drug effects , Up-Regulation/physiology , Vibrissae/physiology
3.
Am J Physiol Regul Integr Comp Physiol ; 291(2): R473-80, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16914434

ABSTRACT

Neuropeptide Y (NPY) is a well-characterized neuromodulator in the central nervous system, primarily implicated in the regulation of feeding. NPY, orexins, and ghrelin form a hypothalamic food intake regulatory circuit. Orexin and ghrelin are also implicated in sleep-wake regulation. In the present experiments, we studied the sleep-modulating effects of central administration of NPY in rats. Rats received intracerebroventricular injection of physiological saline or three different doses of NPY (0.4, 2, and 10 microg in a volume of 4 microl) at light onset. Another group of rats received bilateral microinjection of saline or 2 microg NPY in the lateral hypothalamus in a volume of 0.2 microl. Sleep-wake activity and motor activity were recorded for 23 h. Food intake after the control and treatment injections was also measured on separate days. Intracerebroventricular and lateral hypothalamic administration of NPY suppressed non-rapid-eye-movement sleep and rapid-eye-movement sleep in rats during the first hour after the injection and also induced changes in electroencephalogram delta power spectra. NPY stimulated food intake in the first hour after both routes of administration. Data are consistent with the hypothesis that NPY has a role in the integration of feeding, metabolism, and sleep regulation.


Subject(s)
Neuropeptide Y/administration & dosage , Sleep Stages/drug effects , Wakefulness/drug effects , Animals , Dose-Response Relationship, Drug , Eating/drug effects , Electroencephalography/drug effects , Hypothalamus/physiology , Injections, Intraperitoneal , Injections, Intraventricular , Male , Rats , Rats, Sprague-Dawley
4.
Brain Res ; 1027(1-2): 117-25, 2004 Nov 19.
Article in English | MEDLINE | ID: mdl-15494163

ABSTRACT

We report that mice with a targeted null mutation in the interferon type I receptor (IFN-RI), which cannot respond to such IFNs as IFNalpha and IFNbeta, have a 30% reduction in time spent in spontaneous rapid eye movement sleep (REMS) as a consequence of a reduced number of REMS episodes. Time spent in nonrapid eye movement sleep (NREMS) was essentially unaltered in IFN-RI knockouts (KOs) compared to 129 SvEv controls. Body temperature and locomotor activity were similar in both strains of mice. Hypothalamic expression of mRNAs for molecules previously linked to sleep-wake regulation and an IFN-inducible antiviral gene, 2',5'-oligoadenylate synthetase 1a (OAS), were determined by real-time reverse-transcriptase polymerase chain reaction (RT2-PCR). The level of hypocretin A mRNA was elevated in IFN-RI KO mice compared to 129 SvEv mice, while prolactin mRNA and OAS mRNA levels were suppressed. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) mRNA levels were unchanged relative to controls. Serum prolactin levels were similar in both strains. Results are consistent with the hypothesis that increased hypocretin and reduced prolactin in the hypothalamus of IFN-RI KO mice are responsible for their reduced REMS. In addition, the reduced OAS expression may result in modulation of prolactin receptor signaling and thus contribute to suppression of REMS.


Subject(s)
2',5'-Oligoadenylate Synthetase/metabolism , Gene Expression Regulation/genetics , Hypothalamus/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Neuropeptides/metabolism , Prolactin/blood , Receptors, Interferon/deficiency , Sleep, REM/genetics , Analysis of Variance , Animals , Electroencephalography/methods , Electromyography/methods , Hypothalamus/enzymology , Male , Mice , Mice, Inbred Strains , Mice, Knockout , Orexin Receptors , Orexins , RNA, Messenger/biosynthesis , Receptors, G-Protein-Coupled , Receptors, Interferon/physiology , Receptors, Neuropeptide , Reverse Transcriptase Polymerase Chain Reaction/methods , Time Factors
5.
Am J Physiol Regul Integr Comp Physiol ; 287(5): R1071-9, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15475503

ABSTRACT

To determine the relationships among plasma ghrelin and leptin concentrations and hypothalamic ghrelin contents, and sleep, cortical brain temperature (Tcrt), and feeding, we determined these parameters in rats in three experimental conditions: in free-feeding rats with normal diurnal rhythms, in rats with feeding restricted to the 12-h light period (RF), and in rats subjected to 5-h of sleep deprivation (SD) at the beginning of the light cycle. Plasma ghrelin and leptin displayed diurnal rhythms with the ghrelin peak preceding and the leptin peak following the major daily feeding peak in hour 1 after dark onset. RF reversed the diurnal rhythm of these hormones and the rhythm of rapid-eye-movement sleep (REMS) and significantly altered the rhythm of Tcrt. In contrast, the duration and intensity of non-REMS (NREMS) were hardly responsive to RF. SD failed to change leptin concentrations, but it promptly stimulated plasma ghrelin and induced eating. SD elicited biphasic variations in the hypothalamic ghrelin contents. SD increased plasma corticosterone, but corticosterone did not seem to influence either leptin or ghrelin. The results suggest a strong relationship between feeding and the diurnal rhythm of leptin and that feeding also fundamentally modulates the diurnal rhythm of ghrelin. The variations in hypothalamic ghrelin contents might be associated with sleep-wake activity in rats, but, unlike the previous observations in humans, obvious links could not be detected between sleep and the diurnal rhythms of plasma concentrations of either ghrelin or leptin in the rat.


Subject(s)
Circadian Rhythm/physiology , Food Deprivation/physiology , Leptin/metabolism , Peptide Hormones/metabolism , Sleep Deprivation/metabolism , Sleep/physiology , Animals , Corticosterone/blood , Electrodes, Implanted , Electroencephalography , Feeding Behavior/physiology , Ghrelin , Hypothalamus/metabolism , Leptin/blood , Male , Peptide Hormones/blood , Polysomnography , Rats , Rats, Sprague-Dawley , Sleep, REM/physiology
6.
Phys Rev Lett ; 93(8): 080406, 2004 Aug 20.
Article in English | MEDLINE | ID: mdl-15447163

ABSTRACT

We have measured the precession frequency of a vortex lattice in a Bose-Einstein condensate of Rb87 atoms. The observed mode corresponds to a collective motion in which all the vortices in the array are tilted by a small angle with respect to the z axis (the symmetry axis of the trapping potential) and synchronously rotate about this axis. This motion corresponds to excitation of a Kelvin wave along the core of each vortex and we have verified that it has the handedness expected for such helical waves, i.e., precession in the opposite sense to the rotational flow around the vortices.

7.
Neuroscience ; 124(3): 695-707, 2004.
Article in English | MEDLINE | ID: mdl-14980739

ABSTRACT

Diurnal variations and sleep deprivation-induced changes in the number of Fos-immunoreactive (Fos-IR) neurons in various hypothalamic/preoptic nuclei were studied in the rat. The nuclei implicated in sleep regulation, the ventrolateral preoptic (VLPO), median preoptic (MnPO), and suprachiasmatic (SCN, dorsomedial subdivision) nuclei, displayed maximum c-fos expression in the rest (light) period. Sleep deprivation (S.D.) suppressed Fos-IR in the dorsomedial subdivision of SCN but failed to alter Fos in the VLPO. Fos-IR increased in the VLPO during recovery after S.D. A nocturnal rise in Fos expression was detected in the arcuate (ARC), anterodorsal preoptic (ADP) and anteroventral periventricular (AVPV) nuclei whereas the lateroanterior hypothalamic nucleus (LA) and the ventrolateral subdivision of SCN did not display diurnal variations. S.D. stimulated Fos expression in the ARC, ADP, and LA. Statistically significant, albeit modest, differences were noted in the number of Fos-IR cells between males and cycling female (estrus/diestrus) in the VLPO, MnPO, ARC, LA, and AVPV, and the female ADP did not display diurnal variations. Ovariectomy (OVX) was followed by marked reduction in Fos expression in the VLPO, SCN, and AVPV, and the diurnal rhythm decreased in the VLPO, and vanished in the dorsomedial SCN, and AVP. Estrogen administration to OVX female rats stimulated Fos expression in most nuclei, and the lost diurnal variations reoccurred. In contrast, castration of male rats had little effect on Fos expression (slight rises in diurnal Fos in the ARC and ventrolateral SCN). The results suggest that Fos expression is highly estrogen-dependent in many hypothalamic nuclei including those that have been implicated in sleep regulation.


Subject(s)
Circadian Rhythm/physiology , Estrogens/metabolism , Hypothalamus/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Sex Characteristics , Sleep/physiology , Animals , Arcuate Nucleus of Hypothalamus/cytology , Arcuate Nucleus of Hypothalamus/drug effects , Arcuate Nucleus of Hypothalamus/metabolism , Circadian Rhythm/drug effects , Estrogens/pharmacology , Estrus/drug effects , Estrus/physiology , Female , Hypothalamus/cytology , Hypothalamus/drug effects , Immunohistochemistry , Male , Orchiectomy , Ovariectomy , Preoptic Area/cytology , Preoptic Area/drug effects , Preoptic Area/metabolism , Rats , Rats, Sprague-Dawley , Sleep/drug effects , Suprachiasmatic Nucleus/cytology , Suprachiasmatic Nucleus/drug effects , Suprachiasmatic Nucleus/metabolism
8.
J Neuroendocrinol ; 16(2): 113-8, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14763997

ABSTRACT

Changes in growth hormone-releasing hormone (GHRH), GHRH-receptor (R), somatostatin and interleukin (IL)-1beta mRNA levels were determined in fetal rat hypothalamic cultures after administration of IL-1beta (1, 10, 100 ng/ml, 2 h incubation), and in adult rat hypothalamus 5 h after intracerebroventricular injection of IL-1beta (2.5 and 25 ng). IL-1beta stimulated GHRH-R mRNA expression both in vitro (10 and 100 ng/ml) and in vivo (2.5 and 25 ng). Somatostatin mRNA was significantly stimulated and GHRH mRNA slightly reduced in vitro, while these mRNA species were not altered in vivo in response to IL-1beta. IL-1beta stimulated its own expression both in vitro (10 and 100 ng/ml) and in vivo (25 ng). IL-1beta-induced mRNA responses occurred 2 h after treatment in vitro (incubation times, 30 min to 6 h). IL-1beta also elicited slight GHRH releases in vitro. Up-regulation of hypothalamic GHRH-R by IL-1beta may explain previous findings suggesting that IL-1beta stimulates GHRH activity.


Subject(s)
Growth Hormone-Releasing Hormone/metabolism , Hypothalamus/metabolism , Interleukin-1/physiology , Receptors, Neuropeptide/metabolism , Receptors, Pituitary Hormone-Regulating Hormone/metabolism , Somatostatin/metabolism , Animals , Cells, Cultured , Fetus , Growth Hormone-Releasing Hormone/genetics , Hypothalamus/cytology , Male , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Receptors, Neuropeptide/genetics , Receptors, Pituitary Hormone-Regulating Hormone/genetics , Somatostatin/genetics , Up-Regulation
9.
Neurosci Lett ; 329(1): 69-72, 2002 Aug 23.
Article in English | MEDLINE | ID: mdl-12161265

ABSTRACT

Previous experiments suggest that sleep deprivation (SD) is associated with growth hormone-releasing hormone (GHRH) release and that GHRH promotes sleep via intrahypothalamic sites of action. Binding of [His(1), (125)I-Tyr(10), Nle(27)]hGHRH(1-32) amide and GHRH receptor (GHRH-R) mRNA levels were determined in the hypothalamus and pituitary of rats subjected to 8 h of SD and of undisturbed control rats. The characteristics of the hypothalamic GHRH binding sites differed from those of the pituitary. High affinity GHRH binding and GHRH-R mRNA levels decreased by 50% in the hypothalamus of SD rats, whereas there were no alterations in the pituitary. The results demonstrate that GHRH-Rs exist in the hypothalamus and they respond differently to SD than the GHRH-Rs in the pituitary. The SD-induced changes are explained by down-regulation of the hypothalamic GHRH-Rs induced by GHRH release during and after SD.


Subject(s)
Growth Hormone-Releasing Hormone/analogs & derivatives , Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , Receptors, Neuropeptide/metabolism , Receptors, Pituitary Hormone-Regulating Hormone/metabolism , Sleep Deprivation/metabolism , Animals , Gene Expression/physiology , Growth Hormone-Releasing Hormone/metabolism , Growth Hormone-Releasing Hormone/pharmacology , Hypothalamo-Hypophyseal System/physiopathology , Male , Pituitary-Adrenal System/physiopathology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Receptors, Neuropeptide/genetics , Receptors, Pituitary Hormone-Regulating Hormone/genetics , Sleep Deprivation/physiopathology
10.
Am J Physiol Regul Integr Comp Physiol ; 282(1): R70-6, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11742825

ABSTRACT

The effects of chronic excess of growth hormone (GH) on sleep-wake activity was determined in giant transgenic mice in which the metallothionein-1 promoter stimulates the expression of rat GH (MT-rGH mice) and in their normal littermates. In the MT-rGH mice, the time spent in spontaneous non-rapid eye movement sleep (NREMS) was enhanced moderately, and rapid eye movement sleep (REMS) time increased greatly during the light period. After a 12-h sleep deprivation, the MT-rGH mice continued to sleep more than the normal mice, but there were no differences in the increments in NREMS, REMS, and electroencephalogram (EEG) slow-wave activity (SWA) during NREMS between the two groups. Injection of the somatostatin analog octreotide elicited a prompt sleep suppression followed by increases in SWA during NREMS in normal mice. These changes were attenuated in the MT-rGH mice. The decreased responsiveness to octreotide is explained by a chronic suppression of hypothalamic GH-releasing hormone in the MT-rGH mice. Enhancements in spontaneous REMS are attributed to the REMS-promoting activity of GH. The increases in spontaneous NREMS are, however, not consistent with our current understanding of the role of somatotropic hormones in sleep regulation. Metabolic, neurotransmitter, or hormonal changes associated with chronic GH excess may indirectly influence sleep.


Subject(s)
Growth Hormone/genetics , Growth Hormone/metabolism , Sleep Deprivation/physiopathology , Sleep, REM/physiology , Animals , Electroencephalography , Female , Hormones/pharmacology , Hypothalamus/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Octreotide/pharmacology , Sleep, REM/drug effects
11.
J Pharmacol Exp Ther ; 299(3): 1095-105, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11714899

ABSTRACT

Pregabalin, an analog of gamma-aminobutyric acid (GABA) that does not interact with GABA receptors, is in development as an analgesic, an anticonvulsant, and an anxiolytic. We evaluated the potential somnogenic actions of pregabalin in rats and compared it to those of triazolam, a widely used hypnotic. Pregabalin increased the duration of nonrapid eye movement sleep (NREMS) and decreased rapid eye movement sleep (REMS) after either dark onset or light onset administration. Triazolam increased duration of NREMS and had no effect on duration of REMS. Pregabalin markedly increased the duration of NREMS episodes and decreased the number of NREMS episodes. Power spectrum analysis revealed pregabalin-induced dose-dependent increases in relative delta power after administration. In contrast, triazolam decreased electroencephalographic power density in low frequency bands. Results suggest that pregabalin is a potential sleep modulating agent.


Subject(s)
Eye Movements/drug effects , Sleep/drug effects , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/pharmacology , Animals , GABA Modulators/administration & dosage , GABA Modulators/pharmacology , Male , Pregabalin , Rats , Rats, Sprague-Dawley , Triazolam/administration & dosage , Triazolam/pharmacology , gamma-Aminobutyric Acid/administration & dosage
12.
Neurosci Lett ; 315(1-2): 37-40, 2001 Nov 23.
Article in English | MEDLINE | ID: mdl-11711209

ABSTRACT

Rats were injected intracerebroventricularly with the somatostatin analog, octreotide (OCT; 0.1 microg) or vehicle, and hypothalamic contents of growth hormone-releasing hormone (GHRH), angiotensin II, and vasopressin were determined 10 min, 1, 3 and 6 h post-injection. OCT elicited an immediate release of angiotensin II (10 min) and a rise in GHRH content (1 h) followed by gradual (1-6 h) depletion of accumulated GHRH. Hypothalamic vasopressin was not altered but decreases in pituitary vasopressin occurred 10 min post-injection. The OCT-induced alterations in GHRH may explain previously reported changes in sleep whereas angiotensin may mediate OCT-induced drinking, vasopressin secretion and rises in blood pressure via sst2 somatostatin receptors.


Subject(s)
Angiotensin II/metabolism , Growth Hormone-Releasing Hormone/metabolism , Hypothalamus/drug effects , Octreotide/pharmacology , Animals , Hypothalamus/metabolism , Injections, Intraventricular , Male , Radioimmunoassay , Rats , Rats, Sprague-Dawley , Vasopressins/metabolism
13.
J Neuroimmunol ; 119(2): 192-8, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11585621

ABSTRACT

Although the somnogenic actions of interferon-alpha (IFNalpha) and IFNbeta have been reported, the sleep effects of IFNgamma remained unknown. Thus, we investigated the effects of intracerebroventricular injection of human IFNgamma on sleep in rabbits. IFNgamma dose-dependently increased nonrapid eye movement sleep (NREMS), electroencephalographic slow wave activity and brain temperature (Tbr). These effects were markedly attenuated after the heat treatment of IFNgamma. IFNgamma suppressed rapid eye movement sleep if given during the light period, but not if given at dark onset. Although a tumor necrosis factor receptor fragment did not affect any sleep parameters when given at dark onset, it significantly attenuated IFNgamma-induced NREMS and Tbr. These data suggest that IFNgamma may be involved in the sleep responses during infection. Further, IFNgamma may have a synergistic interaction with intrinsic TNFalpha in the brain.


Subject(s)
Interferon-gamma/pharmacology , Peptide Fragments/pharmacology , Receptors, Tumor Necrosis Factor/immunology , Sleep Stages/drug effects , Sleep Stages/immunology , Amino Acid Sequence , Animals , Body Temperature , Fever/chemically induced , Fever/immunology , Fever/physiopathology , Injections, Intraventricular , Male , Molecular Sequence Data , Peptide Fragments/chemistry , Rabbits , Receptors, Tumor Necrosis Factor/chemistry
14.
Am J Physiol Regul Integr Comp Physiol ; 281(3): R828-38, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11506998

ABSTRACT

Interleukin (IL)-1beta is involved in physiological sleep regulation. IL-18 is a member of the IL-1 family, and its signal-transduction mechanism is similar to that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected intracerebroventricularly (icv) into rabbits at the onset of the dark period. The two higher doses of IL-18 markedly increased non-rapid eye movement sleep (NREMS), accompanied by increases in brain temperature (Tbr). These effects were lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during the light period also increased NREMS and Tbr. Similar results were obtained after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal injection of 30 microg/kg of IL-18 slightly, but significantly, increased NREMS, whereas it significantly decreased electroencephalogram slow-wave activity in rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody had little effect on spontaneous sleep in rabbits, although the anti-IL-18 antibody significantly attenuated muramyl dipeptide-induced sleep. These data suggest that IL-18 is involved in mechanisms of sleep responses to infection.


Subject(s)
Interleukin-18/administration & dosage , Sleep/drug effects , Sleep/physiology , Acetylmuramyl-Alanyl-Isoglutamine/administration & dosage , Animals , Antibodies/administration & dosage , Body Temperature/drug effects , Brain/drug effects , Brain/physiology , Darkness , Dose-Response Relationship, Drug , Electroencephalography/drug effects , Fever/chemically induced , Injections, Intraperitoneal , Injections, Intraventricular , Interleukin-18/antagonists & inhibitors , Light , Male , Photoperiod , Rabbits , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiology , Sleep Stages/drug effects , Sleep Stages/physiology , Specific Pathogen-Free Organisms
15.
Am J Physiol Regul Integr Comp Physiol ; 281(3): R839-45, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11506999

ABSTRACT

Many theories propose that sleep serves a purpose in synaptic plasticity. We tested the hypothesis, therefore, that manipulation of sleep would affect the expression of molecules known to be involved in synaptic plasticity. mRNA expression of four molecules [brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeleton-associated protein (Arc), matrix metalloproteinase-9 (MMP-9), and tissue plasminogen activator (tPA)] was determined after 8 h of sleep deprivation and after 6 h of a mild increase in ambient temperature, a condition that enhances sleep in rats. After sleep deprivation, BDNF, Arc, and tPA mRNAs in the cerebral cortex increased while MMP-9 mRNA levels decreased. Conversely, after enhanced ambient temperature, BDNF, Arc, and tPA mRNAs decreased while MMP-9 mRNA increased. In the hippocampus, sleep deprivation did not significantly affect BDNF and tPA expression, although Arc mRNA increased and MMP-9 mRNA decreased. Brain temperature enhancement decreased Arc mRNA levels in the hippocampus but did not affect BDNF, MMP-9, or tPA in this area. Results are consistent with the notion that sleep plays a role in synaptic plasticity.


Subject(s)
Neuronal Plasticity , Sleep Deprivation/physiopathology , Synapses/metabolism , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/metabolism , Cytoskeletal Proteins/metabolism , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Nerve Tissue Proteins/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Temperature , Tissue Plasminogen Activator/genetics , Tissue Plasminogen Activator/metabolism
16.
Am J Physiol Regul Integr Comp Physiol ; 281(3): R1004-12, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11507019

ABSTRACT

Interleukin (IL)-15 and -2 share receptor- and signal-transduction pathway (Jak-STAT pathway) components. IL-2 is somnogenic in rats but has not been tested in other species. Furthermore, the effects of IL-15 on sleep have not heretofore been described. We investigated the somnogenic actions of IL-15 in rabbits and compared them with those of IL-2. Three doses of IL-15 or -2 (10, 100, and 500 ng) were injected intracerebroventriculary at the onset of the dark period. In addition, 500 ng of IL-15 and -2 were injected 3 h after the beginning of the light period. IL-15 dose dependently increased non-rapid eye movement sleep (NREMS) and induced fever. IL-15 inhibited rapid eye movement sleep (REMS) after its administration during the light period; however, all doses of IL-15 failed to affect REMS if given at dark onset. IL-2 also dose dependently increased NREMS and fever. IL-2 inhibited REMS, and this effect was observed only in the light period. IL-15 and -2 enhanced electroencephalographic (EEG) slow waves during the initial 9-h postinjection period, then, during hours 10-23 postinjection, reduced EEG slow-wave activity. Current data support the notion that the brain cytokine network is involved in the regulation of sleep.


Subject(s)
Interleukin-15/pharmacology , Interleukin-2/pharmacology , Sleep Stages/drug effects , Sleep Stages/physiology , Animals , Circadian Rhythm/drug effects , Circadian Rhythm/physiology , Dose-Response Relationship, Drug , Electroencephalography/drug effects , Injections, Intraventricular , Interleukin-15/administration & dosage , Interleukin-2/administration & dosage , Male , Rabbits
17.
Sleep ; 24(3): 261-6, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11322707

ABSTRACT

STUDY OBJECTIVES: Determine the effects of time of day and sleep deprivation on glutamate decarboxylase 67,000 MW (GAD67) mRNA during cortical synaptic reorganization induced by a unilateral trimming of the mystacial vibrissae in rats. DESIGN: Two experiments were conducted--One measured GAD67 mRNA in the barrel cortex at 3 or 6 h after a unilateral whisker cut at either light or dark onset; the other measured GAD67 mRNA after a unilateral whisker cut at light onset with or without sleep deprivation. SETTING: University-based Research Laboratory. PARTICIPANTS: Sprague-Dawley rats (250-350 g). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The reverse transcriptase polymerase chain reaction was used to measure the time of day changes in GAD67 mRNA after a unilateral whisker cut. GAD67 mRNA decreased in the barrel cortex at 3 and 6 h after a whisker trim at dark onset when the rats were mainly awake. No changes were observed in GAD67 mRNA levels after a whisker cut at light onset, a time when the rats mainly sleep. In situ hybridization for GAD67 mRNA supported these findings; no changes in GAD mRNA occurred in layer 4 of the barrel cortex that received input from the mystacial whiskers that were trimmed at light onset. However, when the rats were sleep-deprived, GAD67 mRNA increased in the barrel cortex receiving input from the lip hairs surrounding the trimmed mystacial whiskers. CONCLUSIONS: These data imply that sleep modifies GAD67 mRNA expression and that this effect is dependent upon the nature of the ongoing synaptic reorganization. They support the notion that sleep serves a synaptic function.


Subject(s)
Glutamate Decarboxylase/metabolism , RNA, Messenger/metabolism , Sleep Deprivation/metabolism , Sleep/physiology , Somatosensory Cortex/metabolism , Vibrissae/physiology , Animals , Circadian Rhythm/physiology , Immunohistochemistry , Male , Neuronal Plasticity/physiology , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Synapses/metabolism
18.
J Neurosci ; 21(8): 2912-8, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11306643

ABSTRACT

The somatotropic axis, and particularly growth hormone-releasing hormone (GHRH), is implicated in the regulation of sleep-wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of the dw/dw rats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in the dw/dw rat.


Subject(s)
Dwarfism, Pituitary/metabolism , Growth Hormone-Releasing Hormone/deficiency , Receptors, Neuropeptide/metabolism , Receptors, Pituitary Hormone-Regulating Hormone/metabolism , Signal Transduction , Sleep Disorders, Intrinsic/metabolism , Animals , Circadian Rhythm , Dwarfism, Pituitary/complications , Dwarfism, Pituitary/genetics , Electroencephalography , Growth Hormone/deficiency , Growth Hormone-Releasing Hormone/genetics , Growth Hormone-Releasing Hormone/metabolism , Hypothalamus/metabolism , Male , Pituitary Gland/metabolism , Preoptic Area/metabolism , RNA, Messenger/metabolism , Rats , Rats, Inbred Lew , Rats, Mutant Strains , Receptors, Neuropeptide/deficiency , Receptors, Neuropeptide/genetics , Receptors, Pituitary Hormone-Regulating Hormone/deficiency , Receptors, Pituitary Hormone-Regulating Hormone/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Sleep Deprivation , Sleep Disorders, Intrinsic/complications , Sleep Disorders, Intrinsic/diagnosis , Sleep Stages/genetics
19.
Brain Res ; 898(1): 105-12, 2001 Apr 13.
Article in English | MEDLINE | ID: mdl-11292453

ABSTRACT

Sleep is hypothesized to influence activity-driven changes in the brain microcircuitry. A change in the barrel cortex following the removal of the mystacial whiskers in rats is a model for synaptic plasticity. This model was combined with sleep deprivation and immunoreactivity for nerve growth factor (NGF) was determined. Sleep deprivation for 6 h after light onset significantly increased the number of NGF-immunoreactive pyramidal neurons in layer V of the barrel cortex. However, unilateral trimming of mystacial whiskers did not affect NGF immunoreactivity in the contralateral or ipsilateral barrel cortices when rats were allowed to sleep. If the rats received a unilateral whisker cut at light onset, and subsequently were deprived of sleep, increases in the NGF-immunoreactive neurons were only observed in the barrel cortex on the side that received input from the remaining intact whiskers. In contrast, NGF immunoreactivity on the side contralateral to the cut whiskers decreased in sleep-deprived animals to levels below those observed in the control animals that were allowed to sleep. These results suggest that NGF expression is influenced by the interaction of sleep, afferent input and the nature of ongoing synaptic reorganization. Further, results are consistent with the hypothesis that growth factors, such as NGF, form part of the mechanism responsible for sleep regulation and that they also form one facet of sleep-related synaptic plasticity.


Subject(s)
Nerve Growth Factor/metabolism , Neurons/metabolism , Sleep Deprivation/metabolism , Somatosensory Cortex/metabolism , Vibrissae/physiology , Animals , Immunohistochemistry , Male , Neuronal Plasticity/physiology , Rats , Rats, Sprague-Dawley , Somatosensory Cortex/cytology , Somatosensory Cortex/physiology
20.
Am J Physiol Regul Integr Comp Physiol ; 280(4): R1001-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11247820

ABSTRACT

Various growth factors (e.g., growth hormone-releasing hormone, acidic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, and interleukin-1) are implicated in sleep regulation. It is hypothesized that neuronal activity enhances the production of such growth factors, and they in turn form part of the sleep regulatory mechanism. Glial cell line-derived neurotrophic factor (GDNF) promotes development, differentiation, maintenance, and regeneration of neurons, and its production is induced by well-characterized sleep regulatory substances such as interleukin-1 and tumor necrosis factor. Therefore, we investigated whether GDNF would promote sleep. Twenty-six male Sprague-Dawley rats and 30 male New Zealand White rabbits were surgically implanted with electroencephalogram (EEG) and electromyogram (EMG; rats only) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and on a separate day with one of the following doses of GDNF: 5, 50, and 500 ng in rabbits and 50 and 500 ng in rats. The EEG, brain temperature, EMG (in rats), and motor activity (in rabbits) were recorded for 23 h after the intracerebroventricular injection. GDNF (500-ng dose) increased the time spent in nonrapid eye movement sleep in both rats and rabbits. Rapid eye movement sleep was not affected by the lower doses of GDNF but was inhibited in rabbits after the high dose. EEG slow-wave activity was not affected by GDNF. The current results provide further evidence that various growth factors are involved in sleep regulation.


Subject(s)
Brain/physiology , Electroencephalography/drug effects , Nerve Growth Factors , Nerve Tissue Proteins/pharmacology , Neuroprotective Agents/pharmacology , Sleep/drug effects , Animals , Brain/drug effects , Electromyography/drug effects , Glial Cell Line-Derived Neurotrophic Factor , Humans , Injections, Intraventricular , Male , Nerve Tissue Proteins/administration & dosage , Neuroprotective Agents/administration & dosage , Rabbits , Rats , Rats, Sprague-Dawley , Recombinant Proteins/pharmacology , Sleep/physiology , Sleep Stages/drug effects , Sleep, REM/drug effects , Time Factors
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