Transcriptome Profile in the Mouse Brain of Hepatic Encephalopathy and Alzheimer’s Disease

Abstract

Hepatic encephalopathy (HE) is a chronic metabolic disease accompanied by neuropathological and neuropsychiatric features, including memory deficits, psychomotor dysfunction, depression, and anxiety. Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by tau hyperphosphorylation, excessive amyloid beta (Aβ) accumulation, the formation of fibrillary tangles, hippocampus atrophy, and neuroinflammation. Recent studies have suggested a positive correlation between HE and AD. Some studies reported that an impaired cholesterol pathway, abnormal bile acid secretion, excessive ammonia level, impaired Aβ clearance, astrocytic dysfunction, and abnormal γ-aminobutyric acid GABAergic neuronal signaling in HE may also be involved in AD pathology. However, the mechanisms and related genes involved in AD-like pathology in the HE brain are unclear. Thus, we compared the cortical transcriptome profile between an HE mouse model, bile duct ligation (BDL), and an AD mouse model, the 5×FAD. Our study showed that the expression of many genes implicated in HE is associated with neuronal dysfunction in AD mice. We found changes in various protein-coding RNAs, implicated in synapses, neurogenesis, neuron projection, neuron differentiation, and neurite outgrowth, and non-coding RNAs possibly associated with neuropathology. Our data provide an important resource for further studies to elucidate AD-like pathophysiology in HE patients.

Keywords

• hepatic encephalopathy (HE)
• Alzheimer’s disease (AD)
• bile duct ligation (BDL) model
• 5×FAD model
• RNA sequencing