Peroxisome proliferator-activated receptor-γ activation attenuates motor and cognition impairments induced by bile duct ligation in a rat model of hepatic cirrhosis

Abstract

Introduction: Hepatic cirrhosis (HC) is a common health problem with long-term consequences. Patients suffering from HC have been shown to have mental and cognitive impairments. Animal models of HC also confirm such impairments. The objective of the current study was to evaluate the possible protective effect of pioglitazone on these impairments in a rat model of HC.

Methods and material: Male Wistar rats were used for the current study. Bile duct ligation (BDL) surgery was performed and pioglitazone (20mg/kg, i.p., once a day) or saline administration was started two weeks after surgery for the next four weeks. Spatial learning (Morris water maze), passive avoidance (PA) learning (shuttle box), balance (rotarod) and muscle strength were evaluated in BDL and sham rats receiving pioglitazone or saline.

Results: BDL rats had an increased level of hepatic enzymes and bilirubin. The increase in hepatic enzymes but not bilirubin by BDL was reversed by pioglitazone. BDL rats showed significant decrease in spatial learning which was reversed by pioglitazone. PA learning was also impaired in BDL rats compared to the other three groups; treatment with pioglitazone reversed these impairments in BDL rats. Balance on the rod was significantly reduced in the BDL and BDL+pioglitazone groups compared to the sham and sham+pioglitazone groups. Muscle strength was not altered in the BDL rats compared to the other two groups.

Conclusion: Results of the current study confirm previous findings regarding the deleterious effect of BDL on cognitive function. Pioglitazone showed promising results against cognitive impairments. Unchanged locomotion indicates that differences observed in spatial and PA learning are not due to motor deficits.

Keywords: Bile duct ligation (BDL); Hepatic cirrhosis; Learning and memory; Motor function; Pioglitazone.