Expression Profile of Hepatic Metallothionein-I and ATP7B, and Brain Metallothionein-III and Acetyl cholinesterase Genes in Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis

Abstract

Cognitive waning due to chronic copper (Cu) intoxication in animal models is increasingly being reported; notwithstanding, information regarding molecular basis of Cu accumulation and neurobehavioral impairments remains fragmentary. Previously, we have shown first in vivo evidence of spatial memory impairments along with astrocytes swelling (Alzheimer type II cells) and astrogliosis (increase in number of astrocytes), Cu deposition in the choroid plexus and degenerated neurons with significant increase in the hippocampus Cu content in Cu-intoxicated Wistar rats. In continuation with our previous study, the aim of this study was to investigate the effects of intraperitoneally injected Cu lactate (0.15 mg Cu/100 g body weight) daily for 90 days on metallothionein–I (MT-I), ATP7B, MT-III and acetylcholinesterase (AChE) gene expression by reverse transcription polymerase chain reaction. Cu-intoxicated group showed significantly increased expression of hepatic MT-I gene compared to control group. However, hepatic ATP7B mRNA levels in Cuintoxicated group were comparable with that of control group. Similarly, MT-III and AChE gene expression in the brain were not significantly altered by chronic Cu-intoxication. In conclusion, the current study demonstrates that chronic Cu toxicity causes increase in hepatic MT-I mRNA levels in male Wistar rats.