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J M Krueger

Publications and source records attributed to J M Krueger.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1998

Changes in sleep in response to intracerebral injection of insulin-like growth factor-1 (IFG-1) in the rat.

Changes in sleep were studied during 6 hours after intracerebroventricular (ICV) administration of Insulin-like growth factor-1 (IGF-1) or the structurally related insulin. IGF-1 was injected either at dark onset (0.05 or 0.5 microgram) or 6 hours after light onset (0.05, 0.5, or 5.0 microgram). The small dose of IGF-1 consistently, albeit modestly, enhanced NREMS over the 6 hour postinjection period in both the dark and the light cycles (REMS increased only at night). The NREMS-promoting activity vanished when the dose was increased to 0.5 microgram, and 5.0 microgram IGF-1 elicited a marked and prompt suppression in NREMS. Heat-inactivated IGF-1 (0.05 microgram) did not alter sleep. On a molar base, the NREMS-promoting dose of insulin was higher than that of IGF-1. Late (hours 7-17 postinjection) enhancements in EEG slow wave activity during NREMS were observed after 5.0 microgram IGF-1. The results indicate that IGF-1 can promote NREMS and may contribute to the mediation of the effects of GH on sleep. The acute sleep-suppressive activity of the high dose of IGF-1 is attributed to an inhibition of endogenous growth hormone-releasing hormone (GHRH).

Analysis of Variance↗
PubMed1998

Effect of sleep deprivation on serum influenza-specific IgG.

Intra-pulmonary protection against influenza virus in immune mice, largely dependent upon serum lgG, is reported to be suppressed by 7 hours of sleep deprivation following viral challenge. This implies that sleep deprivation may accelerate the catabolism of influenza-specific antibodies. To determine the effects of sleep deprivation on the catabolism of serum antibodies, BALB/c mice were passively immunized intravenously with lgG anti-influenza monoclonalantibodies and catabolism kinetics monitored for 6 days. Mice were then sleep-deprived for either 9 hours (one episode) or for 9 hours followed by 6 hours on the consecutive day (two episodes) and the serum titer of influenza-specific monoclonal antibodies monitored for an additional 8 days via ELISA. One episode of sleep-deprivation had only minor effects on lgG catabolism; however, two episodes of sleep-deprivation caused significant changes in the kinetics of lgG catabolism, resulting in elevated lgG levels (p = 0.02) for 2 days post-sleep deprivation. Elevation of serum influenza-specific lgG (p = 0.005) was also seen in actively immune mice following two episodes of sleep-deprivation. Serum chemistries ruled out dehydration as a cause of the increased antibody levels; however, some anomalies were noted: total protein and albumin were elevated, although not significantly, and P and Ca were decreased. Thus, our data do not support the hypothesis that sleep-deprivation lowers existing serum antibody titers by accelerating antibody catabolism.

Animals↗
PubMed1997

Mice lacking the TNF 55 kDa receptor fail to sleep more after TNFalpha treatment.

Tumor necrosis factor (TNF) is a well characterized sleep-regulatory substance. To study receptor mechanisms for the sleep-promoting effects of TNF, sleep patterns were determined in control and TNF 55 kDa receptor knock-out (TNFR-KO) mice with a B6 x 129 background after intraperitoneal injections of saline or murine TNFalpha. The TNFR-KO mice had significantly less baseline sleep than the controls. TNFalpha dose-dependently increased non-rapid eye movement sleep (NREMS) in the controls but did not influence sleep in TNFR-KO mice. Although TNFR-KO mice failed to respond to TNFalpha, they had an increase in NREMS and a decrease in rapid eye movement sleep after interleukin-1beta treatment. These results indicate that TNFalpha affects sleep via the 55 kDa receptor and provide further evidence that TNFalpha is involved in physiological sleep regulation. Current results also extend the list of species to mice in which TNFalpha and interleukin-1beta are somnogenic.

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 variation of TNF alpha in the rat brain.

Tumor necrosis factor-alpha (TNF alpha) is thought to play a physiological role in the brain. These studies were performed to determine whether a diurnal rhythm of TNF alpha exist in the rat brain. Samples were collected from hippocampus, hypothalamus, cerebral cortex, cerebellum, pons and midbrain at light onset and at 6 h intervals thereafter over a day. A TNF alpha bioassay was used to measure TNF alpha in each area. TNF alpha was highest at light onset in the hypothalamus, hippocampus and cerebral cortex. Levels at light onset were about 10-fold greater than minimal night-time levels. Changes in TNF alpha activity in other brain areas were also evident, but smaller. These results support the hypothesis that TNF alpha has physiological roles in the brain.

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

The inhibitory effects of N omega-nitro-L-arginine methyl ester on nitric oxide synthase activity vary among brain regions in vivo but not in vitro.

We studied the effects of intracerebroventricular and intraperitoneal injection and the in vitro effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the nitric oxide synthase activities of the cerebellum, brainstem, hypothalamus, hippocampus, and the remainder of the brain after dissections. Male rats were chronically implanted with lateral icv guide cannula. L-NAME was injected in doses of 0.2, 1, and 5 mg intracerebroventricularly, and 50 mg/kg intraperitoneally. L-NAME induced dose-dependent suppression of NOS activities in each brain region. The threshold dose was 0.2 mg; 1 mg L-NAME completely abolished brain nitric oxide synthase activity 90 min after the injection. Brain NOS activities returned to baseline level 48 h after the injection of 5 mg L-NAME. There were significant differences between the sensitivity of various regions to L-NAME after in vivo but not in vitro administration of the enzyme inhibitor. These findings indicate that intracerebroventricular injection of L-NAME is a useful tool for inhibiting brain nitric oxide synthase activities in vivo. The differences between the sensitivity of different brain regions to L-NAME as well as the relative fast recovery of nitric oxide synthase activities must be taken into account when L-NAME is administered intracerebroventricularly to rats.

Animals↗
PubMed1997

Inhibition of tumor necrosis factor prevents warming-induced sleep responses in rabbits.

Tumor necrosis factor (TNF) is a key regulatory component of sleep. In the present study, we determined the effects of intracerebroventricular injection of a TNF inhibitor, a soluble TNF receptor fragment (TNF-RF), on sleep responses of rabbits during and after exposure to mild increases in ambient temperature (T(amb)). Each rabbit (n = 8) was recorded under three conditions: 1) normal T(amb) (21 degrees C) with pyrogen-free saline (PFS), 50 microl i.c.v.; 2) 27 degrees C T(amb) with PFS, intracerebroventricularly; and 3) 27 degrees C T(amb) with the TNF-RF, 50 microg i.c.v. When T(amb) was increased to 27 degrees C from 21 degrees C, it was kept at that temperature for 6 h after injection. The higher T(amb) alone significantly increased non-rapid eye movement sleep, decreased rapid eye movement sleep, and increased brain temperature (T(br)) across the 23-h recording period. Electroencephalogram slow-wave activity was also significantly enhanced during the 6-h warming period. In contrast, all of the sleep responses associated with the higher T(amb) were absent if rabbits were pretreated with the TNF-RF. The elevated T(br) during the higher T(amb) was not affected by the TNF-RF. The present results suggest that brain TNF is involved in the mild increases in T(amb)-induced sleep responses.

Amino Acid Sequence↗
PubMed1997

Inhibition of brain interleukin-1 attenuates sleep rebound after sleep deprivation in rabbits.

It is hypothesized that interleukin-1 (IL-1) is involved in physiological sleep. If this hypothesis is correct, inhibition of IL-1 should attenuate sleep responses after sleep deprivation. We tested the effect of intracerebroventricular or intravenous injection of an IL-1 inhibitor, an IL-1 receptor fragment (IL-1RF), on sleep rebound after sleep deprivation in rabbits. Six hours of total sleep deprivation significantly increased non-rapid eye movement sleep (NREMS) and enhanced electroencephalogram slow-wave activity during NREMS. Intracerebroventricular treatment with the IL-1RF (50 micrograms) significantly attenuated the sleep responses after sleep deprivation. Furthermore, 1.0 mg/kg i.v. injection of the IL-1RF significantly suppressed spontaneous NREMS in rabbits that were not sleep deprived. However, intravenous administration of the IL-1RF (1.0 mg/kg) failed to attenuate the sleep responses following the 6-h sleep deprivation period. These results support the hypothesis that central pools of IL-1 are important for physiological sleep regulation.

Animals↗
PubMed1997

Subdiaphragmatic vagotomy blocks the sleep- and fever-promoting effects of interleukin-1beta.

The mechanism by which peripheral cytokines signal the central nervous system to elicit central manifestations of the acute phase response remains unknown. Recent evidence suggests that cytokines may signal the brain via the vagus nerve. To test this possibility, we examined sleep-wake activity and brain temperature (Tbr) after the intraperitoneal administration of saline or three doses (0.1, 0.5, and 2.5 microg/kg) of interleukin-1beta (IL-1beta) in subdiaphragmatically vagotomized (Vx) and sham-operated (Sham) rats. The lowest dose of IL-1beta (0.1 microg/kg) increased non-rapid eye movement sleep (NREMS) and slightly elevated Tbr in Sham rats; both responses were blocked in Vx animals. The middle dose tested (0.5 microg/kg) increased NREMS and Tbr in Sham animals; however, in Vx rats, the increase in NREMS was attenuated and the increase in Tbr was blocked. The highest dose of IL-1beta used (2.5 microg/kg) induced increases in NREMS, decreases in rapid eye movement sleep, and a hypothermic response followed by a biphasic fever; these responses were similar in both Sham and Vx rats. These data provide strong evidence that the subdiaphragmatic vagus plays an important role in communicating both sleep and fever signals to the brain. However, there is clearly an alternative pathway by which IL-1 can signal the brain; whether it occurs through activation of other vagal afferents or through direct or indirect actions on the brain remains unknown.

Animals↗
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

Hypothalamic growth hormone-releasing hormone mRNA varies across the day in rats.

Experiments were performed to determine whether growth hormone-releasing hormone (GHRH) mRNA displays diurnal variations in the hypothalamus and cortex of the rat. Levels of GHRH and beta-actin mRNA were measured from hypothalamic and cortical extracts using the reverse transcriptase polymerase chain reaction method in rats sacrificed at 4 h intervals across a 12:12 h light:dark cycle. Hypothalamic GHRH mRNA peaked around the light onset, declined during the light period, and stayed low in the dark. Variations in hypothalamic beta-actin and cortical GHRH mRNA levels were not observed. beta-Actin mRNA expression in the cortex was higher in the dark than in the light period. The results demonstrate that hypothalamic GHRH mRNA displays diurnal variations.

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

Inhibition of tumor necrosis factor attenuates physiological sleep in rabbits.

The involvement of tumor necrosis factor (TNF) in sleep regulation was investigated by blocking TNF using a synthetic TNF receptor fragment (TNFRF) in rabbits. Intracerebroventricular injection of 50 micrograms TNFRF decreased spontaneous non-rapid-eye-movement (NREM) sleep across the 21 h recording period. After 6 h of sleep deprivation (SD), both duration of NREM sleep and electroencephalographic (EEG) slow wave activity during NREM sleep were enhanced. TNFRF suppressed SD-enhanced NREM sleep and EEG slow wave activity. SD per se did not affect rapid-eye-movement (REM) sleep, but TNFRF treatment increased REM sleep after SD. These results are consistent with the hypothesis that TNF is involved in the regulation of physiological NREM sleep.

Amino Acid Sequence↗