The research from the University of Bristol, which was published in PNAS, indicates that there is a lot of room for developing medications that may be used to treat specific memory issues. The most often given anti-inflammatory medication for treating a variety of illnesses, such as allergies, asthma, arthritis, and inflammatory bowel disease, is glucocorticoids, also referred to as steroids.  However, they frequently have negative effects on mood, sleep, and memory, and many patients who are administered steroids experience memory loss and cognitive deterioration.

Dr. Becky Conway-Campbell's multidisciplinary research team at the University of Bristol intended to investigate how steroid therapy affected memory functions to determine if the observed negative effects were due to the steroid or the underlying medical issue. The scientists used a mouse model to discover that even a very brief course of prescription steroids—methylprednisolone for five days—was associated with decreased memory function while completing a task that involved learning and memory.

The hippocampus, a part of the brain crucial for memory and learning, was shown to have undergone considerable changes as a result of the therapy, according to a study of the mouse model brains. The mouse model treated with methylprednisolone showed severely reduced functional activity of the hippocampus as evaluated by electrophysiological recordings, offering the first proof of an underlying reason for the memory loss.

"People who are administered steroids frequently suffer memory problems," said Dr. Matthew Birnie, first author of the study and Fellow at the University of California. "The gene expression component of the work was done while his PhD at the University of Bristol. It has proven challenging to determine if this is a side effect of the actual medication or the outcome of the underlying medical condition.

"Our results offer novel understandings of the effect of steroid therapy on memory functions in the absence of underlying pathologies. Importantly, these data highlight how crucial it is to coordinate a medical treatment plan with endogenous steroid release.

"We have demonstrated how crucial it is to record the times in which you do any experiments," said LINE, a division of the University of Bristol's Department of Neuroscience and Endocrinology. We have demonstrated that the phenomena of synaptic potentiation in the hippocampus only occurs during the active period of day and not during sleep in our model of memory that examines synaptic plasticity, the way neurons communicate to each other.

Additionally, we've demonstrated that long-term steroid use can reduce its efficacy at all times of day and may be a factor in the common steroid user's brain fog. "The strength of the study is due to the excellent multidisciplinary team here at Bristol Medical School and Department of Physiology, Pharmacology and Neuroscience, particularly the rising star young scientist and co-first author of the paper, Dr Matthew Claydon, who performed the electrophysiological experiments in Dr Zuner Bortolotto's lab," continued Dr. Conway-Campbell, Research Fellow in the Translational Health Sciences group at Bristol Medical School.

"Our study's findings may finally help to explain the molecular basis for memory deficits associated with steroid treatment and chronic stress conditions, as well as lead to the identification of drug treatments that could be tailored to treat these types of memory disorders," the author said in her conclusion.

Numerous neuropsychiatric illnesses are connected with disrupted circadian activity. Adrenal glucocorticoid production, which has a distinct reawakening peak and controls metabolic, immunological, and cardiovascular processes as well as mood and cognitive function, is a key coordinator of circadian biological systems. Memory loss following corticosteroid medication is frequently linked to the loss of this circadian rhythm. Unexpectedly, the processes behind this impairment are unknown.

In this study, we reveal that intra hippocampal circadian transcriptional clock-mediated circadian control of the hippocampus transcriptome integrates critical functional networks that relate corticosteroid-inducible gene regulation to synaptic plasticity processes in rats. Furthermore, corticosteroid therapy administered using a 5-day oral dosage treatment procedure had a substantial negative influence on these circadian hippocampus functions.

Memory impairment in hippocampus-dependent behavior was caused by the circadian-entraining signals' misalignment with the hippocampal transcriptome's rhythmic expression and the circadian control of synaptic plasticity.

These findings identify a molecular basis for memory deficits in patients receiving long-acting synthetic corticosteroids and offer mechanistic insights into how corticosteroid exposure influences the transcriptional clock machinery within the hippocampus, leading to adverse effects on critical hippocampal functions.