Subsequent maternal sleep deprivation aggravates neurobehavioral abnormalities, inflammation, and synaptic function in adult male mice exposed to prenatal inflammation

Abstract

ObjectiveStudies have suggested that prenatal exposure to inflammation increases the risk of neuropsychiatric disorders, including anxiety, depression, and cognitive dysfunction. Because of anatomical and hormonal alterations, pregnant women frequently experience sleep dysfunction, which can enhance the inflammatory response. The aim of this study was to explore the effects of maternal sleep deprivation on prenatal inflammation exposure-induced behavioral phenotypes in offspring and identify the associated mechanisms.MethodsPregnant mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15 and were subsequently subjected to sleep deprivation during gestational days 15–21. Anxiety-like behavior was evaluated by the open field test and the elevated plus maze test. Depression-like behavior was assessed by the tail suspension test and the forced swimming test. Cognitive function was determined using the Morris water maze test. The levels of markers of inflammation and synaptic function were examined employing general molecular biological techniques.ResultsThe results showed that prenatal exposure to LPS resulted in anxiety- and depression-like symptoms and learning and memory deficits, and these effects were exacerbated by maternal sleep deprivation. Furthermore, maternal sleep deprivation aggravated the prenatal LPS exposure-induced increase in the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and decrease in the levels of postsynaptic density-95 and synaptophysin in the hippocampus.DiscussionCollectively, these results suggested that maternal sleep deprivation exacerbates anxiety, depression, and cognitive impairment induced by prenatal LPS exposure, effects that were associated with an inflammatory response and synaptic dysfunction.

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane‐exposed offspring mice

“…Recent evidence supports that the expression levels of pro‐inflammatory cytokines and synaptic plasticity–associated proteins are significantly related to cognitive deficits (Zhang, Zhang, Wei et al., 2023 ). Upregulated concentrations of pro‐inflammatory cytokines and downregulated levels of anti‐inflammatory cytokines in the blood are associated with scores of cognitive function in patients with cognitive impairment (Huang et al., 2022 ).…”

“…Pregnant women must inhale anesthesia in specific situations, which can lead to sleep disorders during the perioperative period. We previously reported that MSD exacerbated the adverse effects of prenatal lipopolysaccharide exposure on cognitive function in offspring mice (Zhang, Zhang, Wei et al., 2023 ). In the present study, offspring mice exposed to isoflurane prenatally and whose mothers were concomitantly subjected to SD (MISO + MSD group) had longer latency and distances to locate the hidden platform in the learning phase of the MWM test, and also had a lower percentage of the total distance and time spent in the target quadrant when compared with offspring mice from the MISO group.…”

“…The variations of above expression lead to diminished neurogenesis and subsequent behavioral abnormalities (Han et al., 2020 ; Yao et al., 2022 ). Furthermore, previous studies revealed that MSD markedly downregulated the hippocampal expression of synaptic plasticity–associated proteins in offspring, such as PSD‐95, SYN, and BDNF (Pardo et al., 2016 ; Zhang, Wei, Li et al., 2023 ).…”

“…Owing to the anatomical, psychological, and hormonal changes that occur in late pregnancy, mothers‐to‐be frequently suffer from sleep disorders (Facco et al., 2022 ). Sleep deprivation (SD) during pregnancy could induce pro‐inflammatory effects (Entringer et al., 2010 ) and impaired synaptic plasticity and cognitive behavior in rodents (Wei et al., 2022 ; Zhang, Wei, Ni et al., 2023 ; Zhao et al., 2015 ). The expression levels of pro‐inflammatory cytokines (such as IL‐1β, IL‐6, and tumor necrosis factor‐alpha [TNF‐α]) were enhanced, whereas the expression levels of anti‐inflammatory cytokines (including IL‐10) were reduced in offspring of dams exposed to maternal SD (MSD).…”