2026-10-11T07:42:30Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34003692 2026-09-26T16:20:07Z category_24748 item_type_3 month_year_09_2026

Inflammation-Responsive Transthyretin Links Neuroimmune Adaptation to Cognitive Resilience During Aging Zhi Xu (25110537) Neurosciences not elsewhere classified Neuroinflammation Microglia Transthyretin Gut-brain axis Bacterial outer membrane vesicles Alzheimer’s disease <p dir="ltr">The brain must adapt to peripheral inflammatory stress while preserving neurovascular and cognitive function, but the endogenous mechanisms that coordinate this response remain incompletely understood. Here, we investigated transthyretin (TTR) as an inflammation-responsive component of hippocampal neuroimmune adaptation and examined how this response changes with persistent microbial stress and aging. During acute intestinal inflammation, hippocampal TTR induction closely paralleled microglial inflammatory activation. In vitro, bacterial outer membrane vesicles (OMV) induced inflammatory cytokine expression and increased TTR protein in neurovascular cells, while TNF-α directly induced TTR in microglia and brain endothelial cells. Hippocampal TTR overexpression elicited transcriptional programs enriched for innate immune sensing, host defense, antigen processing, and chemokine signaling, indicating that TTR can actively shape the local immune response. In contrast to the inducible response observed during acute challenge, chronic OMV exposure reduced hippocampal TTR and increased blood-brain barrier (BBB) permeability. Aging was likewise associated with lower hippocampal TTR and loss of the dynamic TTR and BBB responses to intestinal inflammation. Functionally, sustained hippocampal TTR supplementation improved spatial working memory in aged mice, with a trend toward improved recognition memory. Together, these findings identify TTR as an inflammation-responsive regulator of hippocampal immune adaptation whose inducibility is attenuated by persistent microbial stress and aging. This loss of adaptive TTR responsiveness may contribute to declining neurovascular and cognitive resilience with age.</p> 2026-09-26T16:20:07Z Dataset Dataset 10.6084/m9.figshare.34003692.v1 https://figshare.com/articles/dataset/Inflammation-Responsive_Transthyretin_Links_Neuroimmune_Adaptation_to_Cognitive_Resilience_During_Aging/34003692 CC BY 4.0