Summary: Disrupting circadian rhythms during adolescence can change how the brain responds to a prenatal immune challenge, a known risk factor for neurodevelopmental disorders such as schizophrenia and autism. In a controlled mouse study led by McGill University researchers, each factor on its own altered behaviour and brain activity, but their combination produced distinct—and sometimes counterintuitive—effects.
The results highlight that risk factors for brain disorders may interact in complex ways. Circadian disruption does not always worsen outcomes; in some cases it moderates the effects of prenatal inflammation. Because adolescence is a sensitive window for brain development, stable sleep-wake cycles and reduced evening light exposure could be important for long-term brain health.
Key Facts:
- Dual risk interaction: Prenatal infection and adolescent circadian disruption together altered behaviour and gene expression more than either factor alone.
- Unexpected moderation: In some measures, circadian disruption reduced or altered the negative effects associated with prenatal infection.
- Adolescent vulnerability: Teen sleep patterns and evening light exposure may shape long-term neurodevelopmental outcomes.
Source: McGill University
A new McGill University-led mouse study suggests that disrupting the body’s internal clock during adolescence changes how the brain responds to a prenatal immune challenge linked to later-life neurodevelopmental disorders.
Prior epidemiological and experimental work indicates that maternal infection during pregnancy—such as influenza—can increase the offspring’s risk for conditions like schizophrenia and autism. Separately, irregular sleep and circadian rhythm disruption are commonly observed in people with these disorders. The McGill team set out to investigate how these two environmental risk factors interact during early life and adolescence.
In the experiment, pregnant mice were given either a viral mimic (poly I:C) to model maternal immune activation (MIA) or saline, creating prenatal exposure and control groups. Offspring were raised to juvenile and adolescent stages (three to seven weeks old), then assigned to either a normal 12:12 light-dark cycle or to constant light to induce circadian disruption during adolescence. The investigators then measured a suite of behavioural outcomes and performed molecular analyses of brain tissue.
Behavioural testing revealed that both prenatal immune activation and adolescent circadian disruption produced changes in memory, anxiety-like behaviour and social interactions. Importantly, when the two factors were combined the pattern of effects differed from what would be expected if their impacts were simply additive: in some behavioural and molecular measures, constant light exposure during adolescence blunted or altered the consequences of prenatal exposure.
At the molecular level, RNA sequencing of the dorsal hippocampus showed many genes differentially expressed after prenatal poly I:C exposure, particularly in males. However, when adolescent mice experienced both prenatal immune activation and constant light, the number of differentially expressed genes was markedly reduced. Network-level analyses (WGCNA) identified gene modules associated with the treatments, and many hub genes in these modules align with human genes implicated by genome-wide studies in sleep/circadian biology and neurodevelopmental disorders.
The study also found that modules linked to prenatal inflammation and circadian disruption were enriched for microglial signatures, and both factors produced trends in microglia morphology—pointing to possible cellular mechanisms through which environmental insults may shape brain development.
Lead author Tara Delorme, who completed this work as a PhD student at the Douglas Research Centre, emphasized the practical implications: people exposed to multiple risk factors during development may benefit from paying attention to daily rhythms. Senior author Nicolas Cermakian, a professor in McGill’s Department of Psychiatry, noted that adolescents are especially vulnerable because their biological clocks tend to shift later while social demands, like early school start times, remain fixed. Evening exposure to screens and artificial light can further delay rhythms, producing “social jet lag” that may compound developmental risks.
The research team—composed of McGill psychiatry faculty and researchers at the Douglas Mental Health University Institute, including Lalit Srivastava and Patricia Silveira—is now pursuing follow-up work to characterize the specific gene changes and pathways identified in mice and to assess their relevance to human brain development.
Funding:
This research was supported by the Canadian Institutes of Health Research, Velux Stiftung, the Fonds de recherche du Québec, the Ludmer Centre for Neuroinformatics and Mental Health, and the McGill Interdisciplinary Initiative in Infection and Immunity.
About this neurodevelopment research news
Author: Keila DePape
Source: McGill University
Contact: Keila DePape – McGill University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Large-scale effects of prenatal inflammation and early life circadian disruption in mice: Implications for neurodevelopmental disorders” by Tara Delorme et al. Brain, Behavior, and Immunity
Abstract
Large-scale effects of prenatal inflammation and early life circadian disruption in mice: Implications for neurodevelopmental disorders
Approximately 80% of people with neurodevelopmental disorders such as schizophrenia and autism spectrum disorders experience disruptions in sleep or circadian rhythms. This study tested whether environmental circadian disruption during early life interacts with prenatal infection to produce sex-specific behavioural, cellular and molecular deficits in mice.
Pregnant mice received poly I:C or saline at embryonic day 9.5 to model maternal immune activation. Offspring were then exposed during juvenile/adolescent stages to either a standard 12:12 light-dark cycle or to constant light. Behavioural assays revealed significant interactions between prenatal treatment and adolescent lighting in domains of cognition, anxiety and sociability. RNA sequencing of the dorsal hippocampus showed many differentially expressed genes after poly I:C exposure in males; combined exposure to poly I:C and constant light reduced the number of differentially expressed genes. WGCNA revealed modules associated with the treatments, with many hub genes homologous to human genes linked to sleep/circadian regulation and neurodevelopmental disorders. Modules associated with MIA and constant light were enriched for microglial signatures, consistent with observed changes in microglia morphology. Overall, adolescent circadian disruption modulates the consequences of prenatal inflammation at behavioural, cellular and molecular levels in this mouse model.