The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine

Abstract

Bile duct ligation (BDL) in developing rats causes cholestasis, impaired liver function and cognition. Because both nitric oxide (NO) and ammonia are implicated in hepatic encephalopathy (HE), we hypothesized that asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and ammonia affect cognition in young rats with BDL. Four groups of young male Sprague-Dawley rats ages 17 days were used: rat underwent laparotomy (SC group), rat underwent laparotomy plus a 30% ammonium acetate diet (SC+HA group), rat underwent BDL (BDL group), rats underwent BDL plus high ammonia diet (BDL+HA group). Spatial memory was assessed by Morris water maze task. Plasma was collected for biochemical and ADMA analyses. Liver and brain cortex were collected for determination of protein arginine methyltransferase-1 (PRMT1, ADMA-synthesizing enzyme) and dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme). We found BDL group had significantly higher plasma direct/total bilirubin, aspartate aminotransferase, alanine aminotransferase, ADMA, liver p22(phox), and worse spatial performance as compared with SC group. High ammonia diet increased plasma ammonia and ADMA concentration, and aggravated spatial deficit in the presence of BDL-induced cholestasis. We conclude plasma ADMA plays a role in BDL-induced spatial deficit. High ammonia aggravated the spatial deficits encountered in cholestatic young rats.

Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage

“…Hence, we used the Morris Water Maze test to evaluate spatial learning and memory capabilities. Although the number of animals in this study is small, we have previously reported that the Morris Water Maze can assess spatial function in young cholestatic rats [12,26]. Therefore, combined with our previous results, we have clearly demonstrated that young cholestatic rats have spatial deficits that are progressive in nature.…”

The effects of intra-dorsal hippocampus infusion of pregnenolone sulfate on memory function and hippocampal BDNF mRNA expression of biliary cirrhosis-induced memory impairment in rats

“…We also previously demonstratedmemory impairment induced by cirrhosis in rats, using Y-maze test (Javadi-Paydar et al, 2013).Our result is also in direction with other studies which have shown spatial memory impairment in cholestatic rats (Huang et al, 2009, Huang et al, 2010, Hosseini et al, 2013. It also has been demonstrated that the discrimination ability between novel object and experienced sample were impaired in BDL animals ( Pregnenolone sulfate (PREGS) acts as an excitatory neuromodulator and has a variety of neuropharmacological actions like memory enhancement.PREGS increases neuronal activityby inhibiting GABAA receptors (Majewska et al, 1988, Park-Chung et al, 1999 and/or potentiating NMDA receptors (Wu et al, 1991, Park-Chung et al, 1997.…”

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

“…The Morris water maze test was conducted to assess spatial learning and memory [28,29] in all of the groups between PND110 and PND115. The water maze comprised a circular tank (180 cm in diameter, 50 cm high) that was filled with opaque water (24 ± 1°C) to a depth of 25 cm.…”