Authors
Hari Prasad Osuru, Navya Atluri, Tam Le, Jinny Park, Michal Jedrusiak, Elzbieta Dulko, Meghana Illendula, Nadia Lunardi
Published in
Alzheimer's & dementia : the journal of the Alzheimer's Association. Volume 22. Issue 6. Pages e71556.
Abstract
Postoperative delirium (POD) is common in older surgical patients and is clinically associated with an increased risk of long-term cognitive decline and dementia; disrupted BDNF signaling and circadian dysregulation are implicated, but their coordinated mechanisms remain unclear.
Aged male C57BL/6J mice were exposed to anesthesia, surgery, and intensive care unit-like stress (ASI). Hippocampal neuroplasticity, dendritic morphology, epigenetic regulation, and circadian signaling were assessed using molecular assays, imaging, and protein-protein interaction (PPI) network analysis.
ASI reduced brain-derived neurotrophic factor (BDNF)-activity-regulated cytoskeleton-associated protein signaling, dendritic structural complexity, and attention, with accompanying histone hypoacetylation, an increased 5-methylcytosine/5-hydroxymethylcytosine ratio, and disruption of network hubs centered on BDNF and circadian regulators. Suberoylanilide hydroxamic acid mitigated these effects and improved short-term cognitive performance.
Perioperative stress is associated with an epigenetically repressed, synaptically impaired hippocampal state linked to delirium-like behavior and cognitive vulnerability. Targeting chromatin accessibility and BDNF-circadian coupling with histone deacetylase inhibition may mitigate acute cognitive consequences following surgery.
PMID:
42298296
Bibliographic data and abstract were imported from PubMed on 16 Jun 2026.
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