2026-10-13T03:22:43Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33995754 2026-09-25T14:49:15Z category_24748 item_type_3 month_year_09_2026

Gut-derived inflammation engages hippocampaladaptive blood-brain barrier response involving transthyretin Zhi Xu (25110537) Neurosciences not elsewhere classified Intestinal inflammation Blood-brain barrier Neurovascular unit Transthyretin Vascular-associated microglia Alzheimer’s disease <p dir="ltr">Gut-derived inflammatory and microbial signals can disrupt the blood-brain barrier (BBB), but whether the BBB also mounts an adaptive response to these challenges remains poorly understood. Here, we show that acute intestinal inflammation induces a transient, region-selective increase in BBB permeability in the mouse hippocampus followed by barrier recovery. Single-cell transcriptomic analysis identified transthyretin (TTR) as a shared inflammation-responsive candidate across major neurovascular cell populations, and hippocampal TTR protein increased during BBB recovery. Acute exposure to bacterial outer membrane vesicles derived from Alzheimer’s disease (AD)-associated samples increased hippocampal TTR and reduced BBB permeability, whereas chronic exposure to AD-associated microbiota showed the opposite pattern, with reduced TTR accompanying impaired barrier permeability. TTR was also reduced in hippocampal capillaries from individuals with AD. Bidirectional manipulation demonstrated a functional role for TTR in barrier resilience: hippocampal TTR overexpression attenuated inflammation-induced BBB leakage, whereas TTR knockdown increased BBB permeability. At the cellular level, TTR manipulation altered microglia-vascular engagement, and avascular-associated microglial state showed relatively higher Ttrexpression. TTR also promoted endothelial migration and tube formation in vitro, and was associated with endothelial endocytosis, implicating a potential transcellular pathway in barrier regulation. Together, these findings identify TTR as a functional component of an adaptive neurovascular response to gut-derived inflammatory and microbial stress, and reveal BBB resilience as an active dimension of microbiota-gut-brain communication.</p> 2026-09-25T14:49:15Z Dataset Dataset 10.6084/m9.figshare.33995754.v1 https://figshare.com/articles/dataset/Gut-derived_inflammation_engages_hippocampaladaptive_blood-brain_barrier_response_involving_transthyretin/33995754 CC BY 4.0