Growth hormone-releasing hormone: cerebral cortical sleep-related EEG actions and expression

2007 ◽  
Vol 293 (2) ◽  
pp. R922-R930 ◽  
Author(s):  
Éva Szentirmai ◽  
Tadanobu Yasuda ◽  
Ping Taishi ◽  
Mingxiang Wang ◽  
Lynn Churchill ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Eye Movement ◽  
Wave Power ◽  
Growth Hormone Releasing Hormone ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Delta Wave ◽  
Releasing Hormone ◽  
Delta Power

Growth hormone-releasing hormone (GHRH), its receptor (GHRHR), and other members of the somatotropic axis are involved in non-rapid eye movement sleep (NREMS) regulation. Previously, studies established the involvement of hypothalamic GHRHergic mechanisms in NREMS regulation, but cerebral cortical GHRH mechanisms in sleep regulation remained uninvestigated. Here, we show that unilateral application of low doses of GHRH to the surface of the rat somatosensory cortex ipsilaterally decreased EEG delta wave power, while higher doses enhanced delta power. These actions of GHRH on EEG delta wave power occurred during NREMS but not during rapid eye movement sleep. Further, the cortical forms of GHRH and GHRHR were identical to those found in the hypothalamus and pituitary, respectively. Cortical GHRHR mRNA and protein levels did not vary across the day-night cycle, whereas cortical GHRH mRNA increased with sleep deprivation. These results suggest that cortical GHRH and GHRHR have a role in the regulation of localized EEG delta power that is state dependent, as well as in their more classic hypothalamic role in NREMS regulation.

Sleep of transgenic mice producing excess rat growth hormone

2002 ◽  
Vol 282 (1) ◽  
pp. R70-R76 ◽  
Author(s):  
I. Hajdu ◽  
F. Obal ◽  
J. Fang ◽  
J. M. Krueger ◽  
C. D. Rollo
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Eye Movement ◽  
Hormonal Changes ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Rat Growth ◽  
Electroencephalogram Eeg

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.

scholarly journals Spontaneous and influenza virus-induced sleep are altered in TNF-α double-receptor deficient mice

2008 ◽  
Vol 105 (4) ◽  
pp. 1187-1198 ◽  
Author(s):  
Levente Kapás ◽  
Stewart G. Bohnet ◽  
Tim R. Traynor ◽  
Jeannine A. Majde ◽  
Éva Szentirmai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Eye Movement ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Viral Challenge ◽  
Delta Power ◽  
Tnf Α ◽  
Health And Disease ◽  
Factor Α

Tumor necrosis factor-α (TNF-α) is associated with sleep regulation in health and disease. Previous studies assessed sleep in mice genetically deficient in the TNF-α 55-kDa receptor. In this study, spontaneous and influenza virus-induced sleep profiles were assessed in mice deficient in both the 55-kDa and 75-kDa TNF-α receptors [TNF-2R knockouts (KO)] and wild-type (WT) strain controls. Under baseline conditions the TNF-2R KO mice had less non-rapid eye movement sleep (NREMS) than WTs during the nighttime and more rapid eye movement sleep (REMS) than controls during the daytime. The differences between nighttime maximum and daytime minimum values of electroencephalogram (EEG) delta power during NREMS were greater in the TNF-2R KO mice than in WTs. Viral challenge (mouse-adapted influenza X-31) enhanced NREMS and decreased REMS in both strains roughly to the same extent. EEG delta power responses to viral challenge differed substantially between strains; the WT animals increased, whereas the TNF-2R KO mice decreased their EEG delta wave power during NREMS. There were no differences between strains in body temperatures or locomotor activity in uninfected mice or after viral challenge. Analyses of cortical mRNAs confirmed that the TNF-2R KO mice lacked both TNF-α receptors; these mice also had higher levels of orexin mRNA and reduced levels of the purine P2X7 receptor compared with WTs. Results reinforce the hypothesis that TNF-α is involved in physiological sleep regulation but plays a limited role in the acute-phase response induced by influenza virus.

Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation

2006 ◽  
Vol 291 (3) ◽  
pp. E549-E556 ◽  
Author(s):  
P. Schüssler ◽  
A. Yassouridis ◽  
M. Uhr ◽  
M. Kluge ◽  
J. Weikel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Sleep Deprivation ◽  
Eye Movement ◽  
Hormone Secretion ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Corticotropin Releasing Hormone ◽  
Endocrine Activity ◽  
Releasing Hormone ◽  
Recovery Sleep

The neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) regulate sleep and nocturnal hormone secretion in a reciprocal fashion, at least in males. GHRH promotes sleep and GH and inhibits hypothalamo-pituitary-adrenocortical (HPA) hormones. CRH exerts opposite effects. In women, a sexual dimorphism was found because GHRH impairs sleep and stimulates HPA hormones. Sleep deprivation (SD) is the most powerful stimulus for inducing sleep. Studies in rodents show a key role of GHRH in sleep promotion after SD. The effects of GHRH and CRH on sleep-endocrine activity during the recovery night after SD are unknown. We compared sleep EEG, GH, and cortisol secretion between nights before and after 40 h of SD in 48 normal women and men aged 19–67 yr. During the recovery night, GHRH, CRH, or placebo were injected repetitively. After placebo during the recovery night, non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) increased and wakefulness decreased compared with the baseline night. After GHRH, the increase of NREMS and the decrease of wakefulness were more distinct than after placebo. Also, after CRH, NREMS increased higher than after placebo, and a positive correlation was found between age and the baseline-related increase of slow-wave sleep. REMS increased after placebo and after GHRH, but not after CRH. EEG spectral analysis showed increases in the lower frequencies and decreases in the higher frequencies during NREMS after each of the treatments. Cortisol and GH did not differ between baseline and recovery nights after placebo. After GHRH, GH increased and cortisol decreased. Cortisol increased after CRH. No sex differences were found in these changes. Our data suggest that GHRH and CRH augment NREMS promotion after SD. Marked differences appear to exist in peptidergic sleep regulation between spontaneous and recovery sleep.

Sleep deprivation increases rat hypothalamic growth hormone-releasing hormone mRNA

1998 ◽  
Vol 275 (6) ◽  
pp. R1755-R1761 ◽  
Author(s):  
Jianyi Zhang ◽  
Zutang Chen ◽  
Ping Taishi ◽  
Ferenc Obál ◽  
Jidong Fang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Sleep Deprivation ◽  
Mrna Expression ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Mrna Levels ◽  
Growth Hormone Releasing Hormone ◽  
Sleep Regulation ◽  
Releasing Hormone ◽  
Sleep Homeostasis

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.

Epidermal growth factor enhances spontaneous sleep in rabbits

1998 ◽  
Vol 275 (2) ◽  
pp. R509-R514 ◽  
Author(s):  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
Zutang Chen ◽  
Ying Wang ◽  
James M. Krueger
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Eye Movement ◽  
Brain Temperature ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Guide Cannula ◽  
Epidermal Growth

Several growth factors are implicated in sleep regulation. Epidermal growth factor (EGF) is found in the brain, and it influences the production of several sleep-promoting substances. We determined, therefore, whether administration of exogenous EGF affected spontaneous sleep in rabbits. Twenty-five rabbits were implanted with electroencephalographic electrodes, a brain thermistor, and an intracerebroventricular guide cannula. Three doses of EGF (0.5, 5, and 25 μg) were used. The animals were injected intracerebroventricularly with saline as control and one dose of EGF on 2 separate days. Five and twenty-five micrograms of EGF enhanced non-rapid eye movement sleep and increased brain temperature. The 25-μg dose of EGF also inhibited rapid eye movement sleep across the 23-h postinjection recording period. Results are consistent with the hypothesis that EGF, like other growth factors, could be involved in sleep regulation.

Varying photoperiod in the laboratory rat: profound effect on 24-h sleep pattern but no effect on sleep homeostasis

1995 ◽  
Vol 269 (3) ◽  
pp. R691-R701 ◽  
Author(s):  
P. Franken ◽  
I. Tobler ◽  
A. A. Borbely
Keyword(s):  
Eye Movement ◽  
Slow Wave ◽  
Wave Activity ◽  
Slow Wave Activity ◽  
Sleep Pattern ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Marked Rise ◽  
Laboratory Rats

To assess the influence of the photoperiod on sleep regulation, laboratory rats were adapted to a long photoperiod (LPP; 16:8-h light-dark cycle, LD 16:8) or a short photoperiod (SPP; LD 8:16). The electroencephalogram (EEG) and cortical temperature (TCRT) were continuously recorded for a baseline day, a 24-h sleep deprivation (SD) period, and a recovery day. Data obtained previously for LD 12:12 served for comparison. Whereas the photoperiod exerted a prominent effect on the 24-h sleep pattern, the 24-h baseline level of sleep and the response to SD were little affected. Recovery from SD was characterized by a marked rise in rapid eye movement sleep, a moderate rise in non-rapid eye movement sleep, and an initial enhancement of EEG slow-wave activity followed by a decrease below baseline. The amplitude and phase of the "unmasked" 24-h component of TCRT did not differ between LPP and SPP. Computer simulations demonstrated that the changes of TCRT and EEG slow-wave activity can be largely accounted for by the sequence of the vigilance states. We conclude that the photoperiod does not affect the basic processes underlying sleep regulation.

Nuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep

2000 ◽  
Vol 279 (2) ◽  
pp. R404-R413 ◽  
Author(s):  
Takeshi Kubota ◽  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Nuclear Factor Κb ◽  
Current Data ◽  
Interleukin 1Β ◽  
Nuclear Factor ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Cytokine Network ◽  
Inhibitor Peptide

Nuclear factor-κB (NF-κB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1β (IL-1β), tumor necrosis factor-α, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-κB activation would attenuate sleep. A NF-κB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 μg for rats, 100 μg for rabbits). On a separate day, time-matched control injections of a cell-permeable inactive control peptide were done in the same animals. The 50-μg dose of IP in rats and the 100-μg dose in rabbits significantly inhibited non-rapid eye movement sleep and rapid eye movement sleep if administered during the light period. Moreover, pretreatment of rabbits with 100 μg of the IP 12 h before intracerebroventricular injection of IL-1β (10 ng) significantly attenuated IL-1β-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-κB is a crucial factor in physiological sleep regulation.

Interleukin-4 inhibits spontaneous sleep in rabbits

1998 ◽  
Vol 275 (4) ◽  
pp. R1185-R1191 ◽  
Author(s):  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
Ying Wang ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Interleukin 4 ◽  
Light Cycle ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Cytokine Network ◽  
Factor Α ◽  
Physiological Sleep ◽  
Necrosis Factor

Proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α, are involved in sleep regulation. IL-4 is an antiinflammatory cytokine that inhibits proinflammatory cytokine production. The hypothesis that IL-4 should attenuate sleep was studied by determining the effects of IL-4 on rabbit spontaneous sleep. Thirty-six rabbits were used. Four doses of IL-4 (0.25, 2.5, 25, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-4 (25 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were done in the same rabbits on different days. The three highest doses of IL-4 significantly inhibited spontaneous non-rapid eye movement sleep if IL-4 was given during the light cycle. The highest dose of IL-4 (250 ng) also significantly decreased rapid eye movement sleep. On the other hand, IL-4 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-4 provide additional evidence for the hypothesis that a brain cytokine network is involved in the regulation of physiological sleep.

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