Alterations in the intrinsic electrophysiological properties of Purkinje neurons in a rat model of hepatic encephalopathy: Relative preventing effect of PPARγ agonist.

Abstract

Patients suffering from hepatic cirrhosis (HC) have been shown to have motor and cognitive impairments. The cerebellum, which controls coordinated and rapid movements, is a potential target for the deleterious effects of hyperammonemia induced by bile duct ligation. Therefore, the aim of this study was to determine the mechanisms of motor impairments observed in a rat model of HC and second objective of the current study was to evaluate the possible protective effect of pioglitazone (PIO) on these impairments. Male Wistar rats were used in the current study. Bile duct ligation (BDL) surgery was performed and pioglitazone administration was started two weeks after the surgery for the next four weeks. The effects of pioglitazone on BDL-induced electrophysiological changes of the Purkinje cerebellum neurons were evaluated by Whole-cell patch clamp recordings. Purkinje neurons from the BDL group exhibited significant changes in a number of electrophysiological properties and some alterations partially were counteracted by activation of peroxisome proliferator-activated receptor-γ. Purkinje cells from BDL groups showed a significant increase in the spontaneous firing frequency followed by a decrease in the action potential duration of half-amplitude and spike interval. Chronic administration of pioglitazone could contract this effect of BDL on event frequency and interevent interval, though the difference with the sham group was still significant in the duration of action potential. Results of the current study raise the possibility that BDL may profoundly affect the intrinsic membrane properties of the cerebellar Purkinje neurons and PIO administration can counteract some of these effects.