Chronic circadian disruption in adolescent mice impairs hippocampal memory disrupting gene expression oscillations

Abstract

Chronodisruption, 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.

This work was supported by the Ministerio de Ciencia e Innovación, “PID2022-136962OB-100 - MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe”, Ministerio de Sanidad (Delegación del Gobierno para el Plan Nacional sobre Drogas #2023/005 and #Exp2022/008695 Fondos de Recuperación, Transformación y Resiliencia (PRTR) Unión Europea, and by the Generalitat de Catalunya, AGAUR (#2021SGR00485). IGL received a grant from the Ministerio de Ciencia e Innovación (#PRE2020-091923). PBS received a FI-AGAUR grant from the Generalitat de Catalunya (#2021FI-B00205) and was supported by a contract from PID2022-136962OB-100. OV is recipient of an ICREA Academia Award (Institució Catalana de Recerca i Estudis Avançats, Generalitat de Catalunya).