Biology subjects

Pena, F.

Publications and source records attributed to Pena, F..

5 recordsLinked to original sources

bioRxiv2025

Differential effects of postpartum sleep restriction on maternal and offspring immunity in the rat

Backgroundsleep disturbances can trigger a wide range of physiological consequences, affecting hormonal regulation, metabolism, cognitive function, and immune responses. Human mothers worldwide frequently experience sleep restriction and fragmentation, a pattern also observed in other mammalian mothers, such as rats. These alterations may add to sleep disturbances unrelated to motherhood. Considering this, we wondered about the impact of sleep restriction in postpartum mother rats on their immunological status. Furthermore, given that early-life experiences can shape the immune system and that even subtle parental changes can influence offspring development, we hypothesized that maternal sleep loss might also exert detrimental effects on the pups. In this study, we investigated the effects of acute and chronic maternal sleep restriction during the postpartum period on immune parameters in both mother rats and their offspring by analyzing antibody titers and systemic inflammation. Methodsmother rats were surgically implanted with electrodes for polysomnographic recordings and for sleep deprivation (deep electrodes targeting the mesopontine wake-promoting area). From postpartum day 5 to day 9, lactating dams were randomly assigned to one of three groups: chronic sleep restriction (CSR; 6 h of sleep deprivation per day for five consecutive days), acute sleep restriction (ASR; 6 h of sleep deprivation only on postpartum day 9), or control (undisturbed). On postpartum day 9, mothers were milked, and blood samples from both mothers and pups were subsequently collected. ELISA assays quantified IL-17A, IL-6, IgG, and IgG2a in maternal serum; IgG and IgG2a in milk; and IgG in pup serum. Hematological parameters, including leukocyte profiles, were also assessed in peripheral blood of dams and pups. Resultsmaternal immune parameters analyzed remained unaffected by sleep restriction. IgG levels were lower in male pups from mothers subjected to ASR (5560 {+/-} 734 {micro}g/mL) compared with the control group (8666 {+/-} 463 {micro}g/mL; p = 0.025), whereas female pups showed no significant changes. Additionally, both female (4.10 {+/-} 0.58) and male (3.81 {+/-} 0.42) pups from dams subjected to CSR exhibited higher absolute lymphocytes counts relative to the control group (females: 2.28 {+/-} 0.25, p = 0.004; males: 2.44 {+/-} 0.25; p = 0.029). ConclusionsChronic and acute maternal sleep restriction had distinct impacts on offspring immunity, altering serum antibody and leukocyte profiles, while leaving maternal parameters unaffected. These results indicate that maternal sleep loss can influence the offspring even in the absence of detectable maternal immune alterations, with male pups being especially susceptible.

immunology↗

bioRxiv2025

Dual hypocretin receptor antagonism enhances sleep and nursing behavior in lactating rats.

Hypocretins (also known as orexins) are neuropeptides that regulate the sleep-wake cycle and modulate various behaviors, including maternal behavior. They act through two receptor subtypes: hypocretin receptor 1 (HcrtR1) and hypocretin receptor 2 (HcrtR2). Although Dual Orexin Receptor Antagonists (DORAs) are clinically used as hypnotics, most preclinical studies with these drugs have been conducted in males, with limited research in females, leaving the postpartum period largely unexplored. Here, we examined the impact of the DORA Suvorexant on sleep and maternal behavior in lactating rats. Lactating and virgin female rats were implanted with electrodes for polysomnographic recording. Using a counterbalanced design, Suvorexant was orally administered at doses of 0, 10 (SUV10), and 30 mg/kg (SUV30) to virgin rats in diestrus and to lactating rats between postpartum days 4 and 8. Sleep recordings and maternal behaviors were assessed during the light phase for six hours following the administration of the drug. Suvorexant reduced wakefulness and increased slow wave sleep, intermediate state, and REM sleep in both groups, with a stronger effect in virgin females. In lactating rats, Suvorexant increased nursing time and milk ejections, while reducing active maternal behavior such as pup-licking. These findings demonstrate that dual hypocretin receptor antagonism produces hypnotic effects and selectively modulates maternal behavior, promoting nursing while reducing active maternal behavior.

neuroscience↗

bioRxiv2022

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

The medial preoptic area (mPOA) undergoes through neuroanatomical changes across the postpartum period, during which its neurons play a critical role in the regulation of maternal behavior. In addition, this area is also crucial for sleep-wake regulation. We have previously shown that hypocretins (HCRT) within the mPOA facilitate active maternal behaviors in postpartum rats, while the blockade of endogenous HCRT in this area promotes nursing and sleep. To explore the mechanisms behind these HCRT actions, we aimed to evaluate the effects of juxta-cellular HCRT-1 administration on mPOA neurons in urethane-anesthetized postpartum and virgin female rats. We recorded mPOA single units and the electroencephalogram (EEG) and applied HCRT-1 juxta-cellular by pressure pulses. Our main results show that the electrophysiological characteristics of the mPOA neurons and their relationship with the EEG of postpartum rats did not differ from virgin rats. Additionally, neurons that respond to HCRT-1 had a slower firing rate than those that did not. In addition, administration of HCRT increased the activity in one group of neurons while decreasing it in another, both in postpartum and virgin rats. The mechanisms by which HCRT modulate functions controlled by the mPOA involve different cell populations.

neuroscience↗

bioRxiv2021

Role of hypocretin in the medial preoptic area in the regulation of sleep, maternal behavior and body temperature of lactating rats.

The hypocretins (HCRT), also known as orexin, includes two neuroexcitatory peptides, HCRT-1 and HCRT-2 (orexin A y B, respectively), synthesized by neurons located in the postero-lateral hypothalamus, whose projections and receptors are widely distributed throughout the brain, including the medial preoptic area (mPOA). HCRT have been associated with a wide range of physiological functions including sleep-wake cycle, maternal behavior and body temperature, all regulated by the mPOA. Previously we showed that HCRT in the mPOA facilitates certain active maternal behaviors, while the blockade of HCRT-R1 increased the time spent in nursing. As mother rats mainly sleep while they nurse, we hypothesize that HCRT in the mPOA of lactating rats reduce sleep and nursing, while the intra-mPOA administration of the dual orexin receptor antagonist (DORA) would generate the opposite effect. Therefore, the aim of this study was to determine the role of HCRT within the mPOA, in the regulation and integration of the sleep-wake cycle, maternal behavior and body temperature of lactating rats. To evaluate this idea, we assessed the sleep-wake states, maternal behavior and body temperature of lactating rats following microinjections of HCRT-1 (100 and 200 M) and DORA (5mM) into the mPOA. As expected, our data shows that HCRT-1 in mPOA promoted wakefulness and a slightly increase in body temperature, whereas DORA increased both NREM and REM sleep along with nursing and milk ejection. Taken together, our results strongly suggest that the reduction of the endogenous HCRT within the mPOA of lactating rats is important to promote sleep, nursing and milk ejection.

neuroscience↗

bioRxiv2021

Local administration of bicuculline into the ventrolateral and medial preoptic nuclei modifies sleep and maternal behavior in lactating rats.

The preoptic area (POA) is a brain structure classically involved in a wide variety of animal behavior including sleep and maternal care. In the current study, we evaluate the specific effect of disinhibition of two specific regions of the POA, the medial POA nucleus (mPOA) and the ventrolateral POA area (VLPO) on sleep and maternal behavior in lactating rats. For this purpose, mother rats on postpartum day 1 (PPD1) were implanted for polysomnographic recordings and with bilateral cannulae either in the mPOA or in the VLPO. The rats were tested for sleep and maternal behavior on PPD4-8 after the infusion of the GABA-A antagonist, bicuculline (0, 10 or 30 ng/0.2 {micro}l/side). Infusion of bicuculline into the mPOA augmented retrieving and nest building behaviors and reduced both nursing and milk ejections but had almost no effect on sleep. When bicuculine was microinjected into the VLPO, the rats significantly increase the number of retrievings and mouthings and reduced the nursing time without changes in milk ejections, which was associated with an increase in wakefulness and a reduction in light sleep. Our results show that disinhibition of the mPOA, a key area in the control of maternal behavior, increased active maternal behaviors and reduced nursing without affecting wakefulness or sleep time. In contrast, the enhancement of some active maternal behaviors when the drug was infused into the VLPO, a sleep-promoting area, with a concomitant increase in wakefulness suggests that mother rats devote this additional waking time in the active maternal care of the pups. We hypothesize that maternal behavior changes after bicuculine microinjection into the VLPO is caused by a reduction in the sleep drive, rather than a direct effect on maternal behavior.

neuroscience↗