Gallego-Landin, InesBerbegal-Sáez, PaulaValverde Granados, Olga2025-09-162025-09-162025Gallego-Landin I, Berbegal-Sáez P, Valverde O. Chronic circadian disruption in adolescent mice impairs hippocampal memory disrupting gene expression oscillations. Sci Rep. 2025 Jul 19;15(1):26291. DOI: 10.1038/s41598-025-12237-72045-2322http://hdl.handle.net/10230/71205Chronodisruption, the misalignment of internal biological systems with external environmental changes, negatively impacts health and cognition. A prevalent form, social jet lag, affects a large portion of adolescents and is associated with reduced academic performance, and impaired emotional regulation. Despite its prevalence, the mechanism by which adolescent chronodisruption results in cognitive deficits remains unexplored. Here, we induced chronic chronodisruption in adolescent mice through light/dark cycle manipulation. We performed a battery of established behavioral tests alongside an analysis of daily rhythms of expression of genes involved in relevant physiological functions. We report that adolescent circadian disruption induces impairments in short-term, social, and spatial memory without prompting anxiety-like behavior. Gene expression analyses revealed altered oscillation patterns of circadian clock genes in the hypothalamus and hippocampus. Furthermore, we identified alterations in daily patterns of genes involved in glucocorticoid and endocannabinoid transmissions as well as synaptic plasticity. This work emphasizes the importance of circadian homeostasis for cognitive function and hippocampal homeostasis. Thus, understanding the mechanism underlying adolescent chronodisruption is essential to better understand its long-term implications for cognitive function and overall health.application/pdfeng© The Author(s) 2025, corrected publication 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-025-12237-7AdolescenceBehaviorChronodisruptionEndocannabinoidsGene expressionMemory impairmentsSocial jet laginfo:eu-repo/semantics/openAccess