Corticosteroid treatment dysregulates perirhinal circadian rhythms and synaptic function in rats
Abstract
Glucocorticoids regulate the stress response, circadian rhythms, and numerous physiological processes, including cognition, cardiovascular function, metabolism, and immunity. Synthetic glucocorticoids (sGCs), such as methylprednisolone (MPL), are widely prescribed for inflammatory and autoimmune disorders, yet their often severe cognitive side effects remain poorly understood. Here, we examine the impact of chronic MPL treatment on circadian regulation and the synaptic proteome in the perirhinal cortex (PRh) of male rats, a region critical for object recognition memory. We find that corticosteroid signaling in the PRh is subject to circadian modulation across the light–dark cycle, and that MPL disrupts this pattern. MPL alters endogenous circadian and ultradian clock gene expression, and proteomic analyses reveals dysregulation of proteins essential for synaptic transmission and plasticity. Electrophysiological recordings demonstrate impaired synaptic signaling, and behavioral testing shows PRh-dependent novel object recognition deficits. These findings highlight a mechanistic link between sGC treatment, circadian disruption, and cognitive impairment, with broad implications for understanding the cognitive side effects of widely used sGC therapies.
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BibTeX
@article{claydon2026corticosteroid,
title = {{Corticosteroid treatment dysregulates perirhinal circadian rhythms and synaptic function in rats}},
author = {Matthew D. B. Claydon and Olly Troy and Matthew T. Birnie and Yvonne M. Kershaw and Gareth R. I. Barker and Kate J. Heesom and E. Clea Warburton and Zuner. A. Bortolotto and Stafford L. Lightman and Becky L. Conway-Campbell},
journal = {Communications Biology},
year = {2026},
month = nov,
doi = {10.1038/s42003-026-11316-3},
url = {https://www.nature.com/articles/s42003-026-11316-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Corticosteroid treatment dysregulates perirhinal circadian rhythms and synaptic function in rats
AU - Matthew D. B. Claydon
AU - Olly Troy
AU - Matthew T. Birnie
AU - Yvonne M. Kershaw
AU - Gareth R. I. Barker
AU - Kate J. Heesom
AU - E. Clea Warburton
AU - Zuner. A. Bortolotto
AU - Stafford L. Lightman
AU - Becky L. Conway-Campbell
PY - 2026
DA - 2026/11/07
JO - Communications Biology
DO - 10.1038/s42003-026-11316-3
UR - https://www.nature.com/articles/s42003-026-11316-3
AB - Glucocorticoids regulate the stress response, circadian rhythms, and numerous physiological processes, including cognition, cardiovascular function, metabolism, and immunity. Synthetic glucocorticoids (sGCs), such as methylprednisolone (MPL), are widely prescribed for inflammatory and autoimmune disorders, yet their often severe cognitive side effects remain poorly understood. Here, we examine the impact of chronic MPL treatment on circadian regulation and the synaptic proteome in the perirhinal cortex (PRh) of male rats, a region critical for object recognition memory. We find that corticosteroid signaling in the PRh is subject to circadian modulation across the light–dark cycle, and that MPL disrupts this pattern. MPL alters endogenous circadian and ultradian clock gene expression, and proteomic analyses reveals dysregulation of proteins essential for synaptic transmission and plasticity. Electrophysiological recordings demonstrate impaired synaptic signaling, and behavioral testing shows PRh-dependent novel object recognition deficits. These findings highlight a mechanistic link between sGC treatment, circadian disruption, and cognitive impairment, with broad implications for understanding the cognitive side effects of widely used sGC therapies.
SN - 2399-3642
ER -