Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats.
ABSTRACT The main systemic disorders resulting from prolonged sleep deprivation in laboratory animals are a negative energy balance, low circulating thyroid hormones, and host defense impairments. Low thyroid hormones previously have been found caused by altered regulation at the level of the hypothalamus with possible pituitary involvement. The present studies investigated the effects of sleep deprivation on other major anabolic hormonal systems. Plasma growth hormone (GH) concentrations and major secretory bursts were characterized. Insulin-like growth factor I (IGF-I) was evaluated as an integrative marker of peripheral GH effector activity. Prolactin (PRL) was assessed by basal concentrations and by stimulating the pituitary with exogenous thyrotropin-releasing hormone. Leptin was studied for its linkage to metabolic signs of sleep loss and its correspondence to altered neuroendocrine regulation in other disease states. Last, plasma corticosterone was measured to investigate the degree of hypothalamic-pituitary-adrenal activation. Sleep deprivation was produced by the disk-over-water method, a well-established means of selective deprivation of sleep and noninterference with normal waking behaviors. Hormone concentrations were determined in sham comparisons and at intervals during baseline and experimental periods lasting at least 15 days in partially and totally sleep-deprived rats. The results indicate that high-amplitude pulses of GH were nearly abolished and that concentrations of GH, IGF-I, PRL, and leptin all were suppressed by sleep deprivation. Corticosterone concentration was relatively unaffected. Features of these results, such as low GH and low IGF-I, indicate failed negative feedback and point to hypothalamic mechanisms as containing the foci responsible for peripheral signs.
- SourceAvailable from: Joseph V Martin[Show abstract] [Hide abstract]
ABSTRACT: Thyroid hormones induce short-latency nongenomic effects in adult brain tissue, suggesting that their acute administration would affect brain activity in intact animals. The influence on EEG-defined sleep of acute restoration of L-3,3'5-triiodothyronine (T3) to a sleep-regulatory brain region, the preoptic region, was examined in hypothyroid rats. Sleep parameters were monitored for 48hours weekly: for 24hours immediately following a control microinjection and for an additional 24hours after a second microinjection including a T3 dose to the preoptic region or lateral ventricle. Male albino rats were implanted with EEG and EMG electrodes, abdominal temperature/activity transponders and unilateral lateral ventricle cannulae or bilateral preoptic region cannulae, and were given 0.02% n-propythiouracil (PTU) in their drinking water for four weeks. For histologically-confirmed bilateral preoptic region cannula placements (N=7), effects of T3 (especially a 3μg dose) were apparent within ten hours of injection as decreases in REM, NREM and total sleep and increases in waking and activity. Minimal effects of lateral ventricle T3 microinjection were demonstrated (N=5). Significant effects due to the time of day on the experimental measures were seen in both lateral ventricle and preoptic region groups, but these effects did not interact with the effect of administered hormone dose. These effects of T3 microinjection to the preoptic region were demonstrated after acute injections and within hours of injection rather than after chronic administration over days.Brain research 04/2013; · 2.46 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: It has been established that sleep deprivation (SD) reduces the proliferation of neuronal precursors in the adult hippocampus. It has also been reported that psychostimulant drugs modulate adult neurogenesis. We examined the modulatory role of two psychostimulant drugs modafinil and caffeine on adult neuronal cell proliferation (NCP) during 48h of total SD. A novel automated cage shaking stimulus was used to induce SD based on animal activity. 5-bromo-2''-deoxyuridine (BrdU; 50mg/kg/day i.p) was injected at the onset of the light phase for two days. Rats were successfully sleep deprived for 85-94% of total time. Stereological analysis showed that both caffeine and modafinil treatment during SD improved number of BrdU positive cells as compared to the SD group. Caffeine treatment during SD, significantly increased early proliferative and post mitotic stages of doublecortin (DCX) positive cells while modafinil treatment during SD, increased intermediate and post mitotic stages of DCX positive cells compared to SD+Vehicle group. Brain-Derived Neurotrophic Factor (BDNF) expression on BrdU positive cells as well as in the dentate gyrus (DG) region was decreased significantly after sleep deprivation. Both caffeine and modafinil significantly improved BDNF expression in the DG region. Modafinil, but not caffeine, significantly decreased hippocampal adenosine level during SD in comparison to the SD+Vehicle group. It may be concluded that caffeine or modafinil treatment during 48h of SD prevents the SD induced decline in neuronal proliferation and differentiation. Caffeine and modafinil induced alterations of NCP during SD may involve modulation of BDNF and adenosine levels.Experimental Neurology 08/2013; · 4.65 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Sleep deprivation (SD) has become a worldwide public health concern due to the many negative health consequences associated with suboptimal sleep. SD has been linked to a catabolic hormone signature, heart disease, hypertension, diabetes, and an increase in morbidity and mortality. Herein, we investigated the effects and mechanism of SD on cardiac and metabolic health and evaluated the impact of exogenously supplied IGF-1 on these symptoms. In the present study, we show that five days of acute SD negatively impacted all of the various indicators of cardiac and metabolic health. All symptoms of SD were ameliorated by daily administration of IGF-1, however. IGF-1 administration also reduced the phosphorylation of Akt and expression of Bax, a promoter of apoptosis. Conversely, the expression of Bcl-2, an inhibitor of apoptosis, was elevated by IGF-1, and all IGF-1 effects were suppressed by the PI3K/Akt inhibitor LY294002, reaffirming the importance of the PI3K/Akt pathway in the maintenance of cardiac and metabolic health.Biochemical and Biophysical Research Communications 01/2014; · 2.41 Impact Factor