scholarly journals Estradiol Influences Adenosinergic Signaling and NREM Sleep Need in Adult Female Rats

2021 ◽  
Author(s):  
Philip C Smith ◽  
Derrick J Phillips ◽  
Ana Pocivavsek ◽  
Carissa A Byrd ◽  
Shaun S Viechweg ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Adult Female ◽  
Dynamic Range ◽  
Fold Increase ◽  
Nrem Sleep ◽  
Female Rats ◽  
Control Treatment ◽  
Extracellular Adenosine ◽  
Recovery Sleep ◽  
Sleep Homeostat

Studies report estradiol (E2) suppresses sleep in females; however, the mechanisms of E2 action remain largely undetermined. Our previous findings suggest that the median preoptic nucleus (MnPO) is a key nexus for E2 action on sleep. Here, using behavioral, neurochemical and pharmacological approaches, we investigated whether E2 influenced the sleep homeostat as well as adenosinergic signaling in the MnPO of adult female rats. During the Light Phase, where rats accumulate the majority of sleep, E2 markedly reduced NREM-SWA (a measure of the homeostatic sleep need). Following 6-hours of sleep deprivation, levels of NREM-SWA were significantly increased compared to baseline sleep. However, the NREM-SWA levels were not different between E2 and control treatment despite a significant increase in wake at the expense of NREM sleep. Analysis of NREM-SWA differences between baseline and recovery sleep following sleep deprivation demonstrated that E2 induced a 2-fold increase in delta power compared to controls suggesting that E2 significantly expanded the dynamic range for the sleep homeostat. Correlated with E2-induced changes in physiological markers of homeostatic sleep was a marked increase in extracellular adenosine (a molecular marker of homeostatic sleep need) during unrestricted and recovery sleep following a 6-hour deprivation. Additionally, E2 blocked the ability of an adenosine A2A receptor agonist (CGS-21680) to increase NREM sleep compared to controls. Thus, taken together, the findings that E2 increased extracellular adenosine content, while blocking A2A signaling in the MnPO suggests a potential mechanism for how estrogens impact sleep in the female brain.

scholarly journals Estradiol influences adenosinergic signaling and nonrapid eye movement sleep need in adult female rats

SLEEP ◽  
2021 ◽  
Author(s):  
Philip C Smith ◽  
Derrick J Phillips ◽  
Ana Pocivavsek ◽  
Carissa A Byrd ◽  
Shaun S Viechweg ◽  
...  
Keyword(s):  
Eye Movement ◽  
Adult Female ◽  
Nrem Sleep ◽  
Female Rats ◽  
Sleep Behavior ◽  
A2a Receptors ◽  
Recovery Sleep ◽  
And Gender ◽  
Physiological Markers ◽  
Adenosine Signaling

Abstract Gonadal steroids and gender are risk factors for sleep disruptions and insomnia in women. However, the relationship between ovarian steroids and sleep is poorly understood. In rodent models, estradiol (E2) suppresses sleep in females suggesting that E2 may reduce homeostatic sleep need. The current study investigates whether E2 decreases sleep need and the potential mechanisms that govern E2 suppression of sleep. Our previous findings suggest that the median preoptic nucleus (MnPO) is a key nexus for E2 action on sleep. Using behavioral, neurochemical, and pharmacological approaches, we tested whether (1) E2 influenced the sleep homeostat and (2) E2 influenced adenosine signaling in the MnPO of adult female rats. In both unrestricted baseline sleep and recovery sleep from 6-h sleep deprivation, E2 significantly reduced nonrapid eye movement (NREM) sleep-delta power, NREM-slow wave activity (NREM-SWA, 0.5–4.0 Hz), and NREM-delta energy suggesting that E2 decreases homeostatic sleep need. However, coordinated with E2-induced changes in physiological markers of homeostatic sleep was a marked increase in MnPO extracellular adenosine (a molecular marker of homeostatic sleep need) during unrestricted and recovery sleep in E2-treated but not oil control animals. While these results seemed contradictory, systemically administered E2 blocked the ability of CGS-21680 (adenosine A2A receptor agonist) microinjected into the MnPO to increase NREM sleep suggesting that E2 may block adenosine signaling. Together, these findings provide evidence that E2 may attenuate the local effects of the A2A receptors in the MnPO, which in turn may underlie estrogenic suppression of sleep behavior as well as changes in homeostatic sleep need.

Sleep after arousal from hibernation is not homeostatically regulated

1999 ◽  
Vol 276 (2) ◽  
pp. R522-R529 ◽  
Author(s):  
Jennie E. Larkin ◽  
H. Craig Heller
Keyword(s):  
Sleep Deprivation ◽  
Brain Function ◽  
Extended Period ◽  
Nrem Sleep ◽  
Wave Activity ◽  
Ground Squirrels ◽  
Recovery Sleep ◽  
Sleep Homeostasis ◽  
Homeostatic Response ◽  
Periodic Arousals

Electroencephalographic slow-wave activity (SWA) in non-rapid eye movement (NREM) sleep is directly related to prior sleep/wake history, with high levels of SWA following extended periods of wake. Therefore, SWA has been thought to reflect the level of accumulated sleep need. The discovery that euthermic intervals between hibernation bouts are spent primarily in sleep and that this sleep is characterized by high and monotonically declining SWA has led to speculation that sleep homeostasis may play a fundamental role in the regulation of the timing of bouts of hibernation and periodic arousals to euthermia. It was proposed that because the SWA profile seen after arousal from hibernation is strikingly similar to what is seen in nonhibernating mammals after extended periods of wakefulness, that hibernating mammals may arouse from hibernation with significant accumulated sleep need. This sleep need may accumulate during hibernation because the low brain temperatures during hibernation may not be compatible with sleep restorative processes. In the present study, golden-mantled ground squirrels were sleep deprived during the first 4 h of interbout euthermia by injection of caffeine (20 mg/kg ip). We predicted that if the SWA peaks after bouts of hibernation reflected a homeostatic response to an accumulated sleep need, sleep deprivation should simply have displaced and possibly augmented the SWA to subsequent recovery sleep. Instead we found that after caffeine-induced sleep deprivation of animals just aroused from hibernation, the anticipated high SWA typical of recovery sleep did not occur. Similar results were found in a study that induced sleep deprivation by gentle handling (19). These findings indicate that the SWA peak immediately after hibernation does not represent homeostatic regulation of NREM sleep, as it normally does after prolonged wakefulness during euthermia, but instead may reflect some other neurological process in the recovery of brain function from an extended period at low temperature.

Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons

2021 ◽  
Vol 118 (47) ◽  
pp. e2111183118
Author(s):  
Jessica E. Schwarz ◽  
Anna N. King ◽  
Cynthia T. Hsu ◽  
Annika F. Barber ◽  
Amita Sehgal
Keyword(s):  
Locomotor Activity ◽  
Sleep Deprivation ◽  
Circadian Clock ◽  
Sleep Loss ◽  
Daily Cycle ◽  
Shaped Body ◽  
Recovery Sleep ◽  
Sleep Homeostat ◽  
Central Clock ◽  
Homeostatic Mechanisms

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide–dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.

scholarly journals Galanin neurons in the hypothalamus link sleep homeostasis, body temperature and actions of the α2 adrenergic agonist dexmedetomidine

2019 ◽  
Author(s):  
Ying Ma ◽  
Giulia Miracca ◽  
Xiao Yu ◽  
Edward C. Harding ◽  
Andawei Miao ◽  
...  
Keyword(s):  
Body Temperature ◽  
Sleep Deprivation ◽  
Core Body Temperature ◽  
Neuronal Cell ◽  
Nrem Sleep ◽  
Temperature Characteristic ◽  
Adrenergic Agonist ◽  
Delta Power ◽  
Recovery Sleep ◽  
Sleep Homeostasis

AbstractSleep deprivation induces a characteristic rebound in NREM sleep accompanied by an immediate increase in the power of delta (0.5 - 4 Hz) oscillations, proportional to the prior time awake. To test the idea that galanin neurons in the mouse lateral preoptic hypothalamus (LPO) regulate this sleep homeostasis, they were selectively genetically ablated. The baseline sleep architecture of LPO-ΔGal mice became heavily fragmented, their average core body temperature permanently increased (by about 2°C) and the diurnal variations in body temperature across the sleep-wake cycle also markedly increased. Additionally, LPO-ΔGal mice showed a striking spike in body temperature and increase in wakefulness at a time (ZT24) when control mice were experiencing the opposite - a decrease in body temperature and becoming maximally sleepy (start of “lights on”). After sleep deprivation sleep homeostasis was largely abolished in LPO-ΔGal mice: the characteristic increase in the delta power of NREM sleep following sleep deprivation was absent, suggesting that LPO galanin neurons track the time spent awake. Moreover, the amount of recovery sleep was substantially reduced over the following hours. We also found that the α2 adrenergic agonist dexmedetomidine, used for long-term sedation during intensive care, requires LPO galanin neurons to induce both the NREM-like state with increased delta power and the reduction in body temperature, characteristic features of this drug. This suggests that dexmedetomidine over-activates the natural sleep homeostasis pathway via galanin neurons. Collectively, the results emphasize that NREM sleep and the concurrent reduction in body temperature are entwined at the circuit level.SignificanceCatching up on lost sleep (sleep homeostasis) is a common phenomenon in mammals, but there is no circuit explanation for how this occurs. We have discovered that galanin neurons in the hypothalamus are essential for sleep homeostasis as well as for the control of body temperature. This is the first time that a neuronal cell type has been identified that underlies sleep homeostasis. Moreover, we show that activation of these galanin neurons are also essential for the actions of the α2 adrenergic agonist dexmedetomidine, which induces both hypothermia together with powerful delta oscillations resembling NREM sleep. Thus, sleep homeostasis, temperature control and sedation by α2 adrenergic agonists can all be linked at the circuit level by hypothalamic galanin neurons.

Natural hypothermia and sleep deprivation: common effects on recovery sleep in the Djungarian hamster

1996 ◽  
Vol 271 (5) ◽  
pp. R1364-R1371 ◽  
Author(s):  
T. Deboer ◽  
I. Tobler
Keyword(s):  
Sleep Deprivation ◽  
Brain Temperature ◽  
Alternative Hypothesis ◽  
Nrem Sleep ◽  
Wave Activity ◽  
Daily Torpor ◽  
Djungarian Hamster ◽  
Subsequent Increase ◽  
Recovery Sleep ◽  
Sleep Debt

Sleep, daily torpor, and hibernation have been considered to be homologous processes. However, in the Djungarian hamster, daily torpor is followed by an increase in slow-wave activity (SWA; electroencephalogram power density 0.75-4.0 Hz) that is similar to the increase observed after sleep deprivation. A positive correlation was found between torpor episode length and the subsequent increase in SWA, which was highest when SWA was assumed to increase with a saturating exponential function. Thus the increase in SWA propensity during daily torpor followed similar kinetics as during waking, supporting the hypothesis that when the animal is in torpor it is incurring a sleep debt. An alternative hypothesis, proposing that the mode of arousal causes the subsequent SWA increase, was tested by warming the animals during emergence from daily torpor. Irrespective of mode of arousal, more non-rapid eye movement (NREM) sleep and a similar SWA increase was found after torpor. The data are compatible with a putative neuronal restorative function for sleep associated with the expression of SWA in NREM sleep. During torpor, when brain temperature is low, this function is inhibited, whereas the need for restoration accumulates. Recovery takes place only after return to euthermia.

scholarly journals PER3 polymorphism and cardiac autonomic control: effects of sleep debt and circadian phase

2008 ◽  
Vol 295 (5) ◽  
pp. H2156-H2163 ◽  
Author(s):  
Antoine U. Viola ◽  
Lynette M. James ◽  
Simon N. Archer ◽  
Derk-Jan Dijk
Keyword(s):  
Sleep Deprivation ◽  
Slow Wave Sleep ◽  
Variable Number Tandem Repeat ◽  
Low Frequency ◽  
Nrem Sleep ◽  
Variable Number ◽  
Sympathovagal Balance ◽  
Coding Region ◽  
Circadian Phase ◽  
Recovery Sleep

A variable number tandem repeat polymorphism in the coding region of the circadian clock PERIOD3 ( PER3) gene has been shown to affect sleep. Because circadian rhythms and sleep are known to modulate sympathovagal balance, we investigated whether homozygosity for this PER3 polymorphism is associated with changes in autonomic nervous system (ANS) activity during sleep and wakefulness at baseline and after sleep deprivation. Twenty-two healthy participants were selected according to their PER3 genotype. ANS activity, evaluated by heart rate (HR) and HR variability (HRV) indexes, was quantified during baseline sleep, a 40-h period of wakefulness, and recovery sleep. Sleep deprivation induced an increase in slow-wave sleep (SWS), a decrease in the global variability, and an unbalance of the ANS with a loss of parasympathetic predominance and an increase in sympathetic activity. Individuals homozygous for the longer allele ( PER3 5/5) had more SWS, an elevated sympathetic predominance, and a reduction of parasympathetic activity compared with PER3 4/4, in particular during baseline sleep. The effects of genotype were strongest during non-rapid eye movement (NREM) sleep and absent or much smaller during REM sleep. The NREM-REM cycle-dependent modulation of the low frequency-to-(low frequency + high frequency) ratio was diminished in PER3 5/5 individuals. Circadian phase modulated HR and HRV, but no interaction with genotype was observed. In conclusion, the PER3 polymorphism affects the sympathovagal balance in cardiac control in NREM sleep similar to the effect of sleep deprivation.

Effects of selective sleep deprivation on ventilation during recovery sleep in normal humans

1992 ◽  
Vol 72 (1) ◽  
pp. 100-109 ◽  
Author(s):  
J. B. Neilly ◽  
N. B. Kribbs ◽  
G. Maislin ◽  
A. I. Pack
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Rem Sleep Deprivation ◽  
Sleep Period ◽  
Recovery Sleep ◽  
The Relationship

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.

Effects of oestradiol and progesterone on stress-induced secretion of prolactin in ovariectomized and/or adrenalectomized female rats

1986 ◽  
Vol 112 (1) ◽  
pp. 79-82 ◽  
Author(s):  
Ljiljana Milenković ◽  
Ljubica Bogić ◽  
Jovo V. Martinović
Keyword(s):  
Single Dose ◽  
Adult Female ◽  
Acute Stress ◽  
Fold Increase ◽  
Female Rats ◽  
Female Rat ◽  
Basal Serum ◽  
Conscious Animals

Abstract. Prolactin (Prl) secretion in response to an acute stress was studied in ovariectomized (OVX) and/or adrenalectomized (ADX) adult female rats, non-treated or injected sc with a single dose of 5 μg oestradiol-17β benzoate (OB) or 2 mg progesterone (P). The stress applied consisted of cutting the tip of tail of conscious animals. Radioimmunoassay was used to measure Prl in the serum prepared from blood collected by decapitation 10 min following the stress, i.e., at the point of maximum recorded Prl response. It was found that the capacity of the animals to secrete large quantities of Prl under stress was, when compared to that in intact controls, markedly reudced in OVX or ADX rats and substantially absent in OVX + ADX rats. A 10-fold increase of basal serum Prl, similar in magnitude to the increase in intact controls, was induced by the stress in OVX animals pretreated with OB. On the contrary, pretreatment of OVX animals with P resulted in a complete block of the Prl response to the stress. The stimulative effect of OB was greatly attenuated in stressed OVX + ADX rats. The results suggest that OB potentiates whereas P attenuates the stress-induced secretion of Prl in the female rat, and that the potentiating effect of OB is dependent on functionally intact adrenals.

Sign in / Sign up

Export Citation Format

Share Document