Corticosteroid treatment dysregulates perirhinal circadian rhythms and synaptic function in rats

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. Research was funded by the Medical Research Council (grant number MR/R010919/1) awarded to S.L.L. Present address: Department of Psychology, Florida State University, Tallahassee, FL, USA These authors contributed equally: Matthew D.

School of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, UK Matthew D. Bortolotto Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Translational Health Sciences, Faculty of Health Sciences, School of Medicine, University of Bristol, Bristol, UK Olly Troy, Matthew T. Conway-Campbell Correspondence to Matthew D.

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