Spatial memory alterations in three models of hepatic encephalopathy

Area of Science:

• Neuroscience
• Gastroenterology
• Behavioral Science

Background:

• Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder associated with liver dysfunction.
• Existing models of HE exhibit varying degrees of cognitive impairment, necessitating detailed behavioral characterization.

Purpose of the Study:

• To behaviorally evaluate chronic models of Type B (portacaval shunt [PCS], portal hypertension [PH]) and Type C (thioacetamide-induced [TAA]) hepatic encephalopathy.
• To investigate the impact of these HE models on locomotion, anxiety, and distinct types of memory (spatial reference and working memory).

Main Methods:

• Utilized three chronic HE models: PCS, PH, and TAA-induced cirrhosis.
• Assessed locomotion using the rotarod-accelerod test.
• Evaluated anxiety via the open field and elevated plus maze tests.
• Measured spatial memory using the Morris water maze.

Main Results:

• Locomotor activity and anxiety levels remained unaffected across all HE models compared to controls.
• PCS and TAA groups exhibited severe deficits in spatial reference memory.
• The PH group showed less severe spatial reference memory impairment but a significant deficit in spatial working memory, similar to the TAA group.

Conclusions:

• Demonstrated a double dissociation in spatial reference and working memory deficits between PCS and PH models.
• These findings highlight distinct cognitive alterations in different HE models, offering valuable insights into the underlying cerebral mechanisms of HE-associated cognitive dysfunction.