Maternal immune activation exerts long‐term effects on activity and sleep in male offspring mice

• Published in: The European journal of neuroscience 2024-10, Vol.60 (7), p.5505-5521
• Main Authors: ElGrawani, Waleed, Mueller, Flavia S., Schalbetter, Sina M., Brown, Steven A., Weber‐Stadlbauer, Ulrike, Tarokh, Leila
• Format: Article
• Language: English
• Subjects: activity; Activity patterns; animal model; Animal models; autism; Circadian rhythms; cytokines; EEG; Immune response; infection; Inflammation; Locomotor activity; maternal immune activation (MIA); NREM sleep; Offspring; poly(I:C); Polyinosinic:polycytidylic acid; Prenatal experience; REM sleep; Risk factors; schizophrenia; Sleep; Sleep and wakefulness; Sleep deprivation; slow waves; spindles
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.16506

Exposure to infectious or non‐infectious immune activation during early development is a serious risk factor for long‐term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic‐polyribocytdilic acid), a synthetic analogue of double‐stranded RNA, during gestation, which robustly induces an acute viral‐like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)‐treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non‐rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)‐exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non‐exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring. We investigated circadian activity and sleep patterns in adult male offspring of maternal immune activation (MIA) mouse model using infrared and EEG recordings. MIA offspring exhibited reduced nighttime activity, prolonged NREM sleep duration and higher density of NREM spindles. Moreover, MIA offspring had longer NREM sleep bouts, with noticeable spectral changes across different frequencies, including increased slow wave activity, under conditions of heightened sleep pressure.