Biology subjects

Benedetto, L.

Publications and source records attributed to Benedetto, L..

4 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↗

bioRxiv2023

Characterizing the power spectrum dynamics of the NREM to REM sleep transition

The transition from NREM to REM sleep is considered a transitional or intermediate stage (IS), characterized by high amplitude spindles in the frontal cortex and theta activity in the occipital cortex. Early reports in rats showed an IS lasting from 1 to 5 s, but recent studies suggested a longer duration of this stage. To further characterize the IS, we analyzed its spectral characteristics on electrocorticogram (ECoG) recordings of the olfactory bulb (OB), motor (M1), somato-sensory (S1) and secondary visual cortex (V2) in twelve Wistar male adult rats. By comparing the IS to consolidated NREM/REM epochs, our results reveal that the IS has specific power spectral patterns that statistically differ from both NREM and REM sleep states. Specifically, the main findings were that sigma (11-16 Hz) and beta (17-30 Hz) power in OB, M1, and S1 increased during the IS compared to NREM and REM sleep and began 55 s before REM sleep onset. Additionally, low gamma (31-48 Hz) in the OB started transitioning from NREM levels to REM ones 65 s before its onset. Finally, the high-frequency oscillations (102-198 Hz) in OB, M1, and S1 showed a power increase that began 40 s before REM sleep and reached REM sleep values 10 s after its onset. Thus, we argue that the NREM to REM transition contains its own spectral profile and is more extended than previously described.

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↗