Exposure to lipopolysaccharide (LPS) during prenatal development leads to various changes in neurobiological and behavioural patterns. Similarly, continuous exposure to constant light (LL) during the critical developmental period of the circadian system affects gene expression in various tissues in adulthood. Given the reciprocal nature of the interaction between the circadian and the immune systems, our study primarily investigated the individual effects of both interventions and, more importantly, their combined effect. We aimed to explore whether there might be a potential synergistic effect on circadian rhythms and their parameters, focussing on the expression of clock genes, immune-related genes, and specific genes in the hippocampus, pineal gland, spleen and adrenal gland of rats at postnatal day 30. Our results show a significant influence of prenatal LPS and postnatal LL on the expression profiles of all genes assessed. However, the combination of prenatal LPS and postnatal LL only revealed an enhanced negative effect in a minority of the comparisons. In most cases, it appeared to attenuate the changes induced by the individual interventions, restoring the measured parameters to values closer to those of the control group. In particular, genes such as Nr1d1, Aanat and Tph1 showed increased amplitude in the pineal gland and spleen, while the kynurenine enzymes Kynu and KatII developed circadian rhythmicity in the adrenal glands only after the combined interventions. Our data suggest that a mild immunological challenge during prenatal development may play a critical role in triggering an adaptive response of the circadian clock later in life.

Department of Physiology Faculty of Science Charles University Prague Czech Republic

National Institute of Mental Health Klecany Czech Republic

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