The Change of Noncoding RNA Expression in Olfactory Bulb of Hepatic Encephalopathy Mouse Model: Transcriptomic Analysis and Cellular Analysis.

Abstract

OBJECTIVES: Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with cirrhosis and chronic liver disease primarily driven by ammonia (NH3) toxicity, which leads to neuroinflammation and cognitive deficits. Recent studies have identified olfactory dysfunction as a potential early indicator of HE, linked to ammonia-induced neurotoxicity in the brain. METHODS: After confirming physiological alterations in olfactory cells induced by ammonia, we assessed gene expression changes in olfactory bulbs of bile duct ligation (BDL) mice as an HE mouse model. We systematically profiled diverse coding and noncoding RNAs (ncRNAs) associated with olfactory dysfunction in HE and analyzed the functional implications based on transcriptomic signatures. We also compared ammonia toxicity effects between the olfactory bulb and cerebral cortex in this animal model. RESULTS: Furthermore, we investigated the differential impacts on the olfactory bulb between HE and high-fat diet-induced models, two major paradigms of metabolic imbalance. We identified key RNAs commonly altered between the olfactory bulb and cerebral cortex of the HE model, as well as in olfactory bulbs across BDL and high-fat diet models. CONCLUSIONS: Our results provide a transcriptomic resource for understanding the molecular landscape of HE-related olfactory dysfunction and may inform future studies aimed at functional validation and therapeutic exploration.