What this means
Minimal hepatic encephalopathy (MHE) is a neurological complication associated with chronic liver disease characterized by subtle cognitive impairment and neuroinflammation, particularly in the aging population. However, the molecular mechanisms underlying age-associated MHE remain poorly understood.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Animals or cells
- Kind of research
- Research in animals or cells
The science
- Original title
- Pharmacological downregulation of Fetuin-A attenuates TLR4-mediated neuroinflammation in aged rats with minimal hepatic encephalopathy.
- Authors
- Singh VV, Thakur P, Prasad SK et al.
- Journal
- Biogerontology
- Published
- Oct 24, 2026
- Study type
- Lab or animal study · indexed as animal research
- PMID
- 42925439 ↗
Abstract
Minimal hepatic encephalopathy (MHE) is a neurological complication associated with chronic liver disease characterized by subtle cognitive impairment and neuroinflammation, particularly in the aging population. However, the molecular mechanisms underlying age-associated MHE remain poorly understood. The present study investigated the role of Fetuin-A-mediated neuroinflammation and its potential as a therapeutic target in the management of MHE in old rats using pioglitazone in a thioacetamide (TAA)-induced MHE model in aged rats. Old male rats were administered TAA (50 mg/kg) for 14 days to induce MHE, followed by pioglitazone treatment (3 mg/kg) for 7 days. Western blot and immunofluorescence analyses revealed elevated hippocampal Fetuin-A expression in MHE rats, accompanied by activation of the TLR4/MyD88/NF-κB signaling pathway and increased inflammatory cytokines (IL-6 and TNF-α). Pioglitazone treatment significantly reduced Fetuin-A expression and was accompanied by reduced TLR4, MyD88 and nuclear NF-κB expression, and by decreased astrocyte activation Furthermore, histological and Golgi-Cox analyses demonstrated restoration of neuronal density, dendritic arborization, and spine density in the hippocampus of pioglitazone-treated old MHE rats. Behavioral analyses further confirmed the molecular and histological findings. Thus, elevated hippocampal Fetuin-A is associated with TLR4/MyD88/NF-κB activation in aged MHE rats, and its pharmacological reduction by pioglitazone is accompanied by reduced neuroinflammation, restored hippocampal cytoarchitecture and recovered recognition memory. A causal role for Fetuin-A remains to be established by direct perturbation.
Singh VV, Thakur P, Prasad SK et al. Pharmacological downregulation of Fetuin-A attenuates TLR4-mediated neuroinflammation in aged rats with minimal hepatic encephalopathy. Biogerontology. 2026. doi:10.1007/s10522-026-10533-x. PMID: 42925439. https://pubmed.ncbi.nlm.nih.gov/42925439/