l-Tyrosine administration increases acetylcholinesterase activity in rats

► Chronic administration of l-tyrosine increased AChE activity. ► Acute administration in 10 and 30-day-old rats increased AChE activity. ► Acute administration in 10-day-old rats decreased mRNA levels of AChE. ► Acute administration in 30-day-old rats decreased mRNA levels of AChE. ► Chronic administration decreased mRNA levels of AChE. Tyrosinemia is a rare genetic disease caused by mutations on genes that codify enzymes responsible for tyrosine metabolism. Considering that tyrosinemics patients usually present symptoms associated with central nervous system alterations that ranges from slight decreases in intelligence to severe mental retardation, we decided to investigate whether acute and chronic administration of l-tyrosine in rats would affect acetylcholinesterase mRNA expression and enzymatic activity during their development. In our acute protocol, Wistar rats (10 and 30days old) were killed one hour after a single intraperitoneal l-tyrosine injection (500mg/kg) or saline. Chronic administration consisted of l-tyrosine (500mg/kg) or saline injections 12h apart for 24days in Wistar rats (7days old) and rats were killed 12h after last injection. Acetylcholinesterase activity was measured by Ellman’s method and acetylcholinesterase expression was carried out by a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay. We observed that acute (10 and 30days old rats) and chronic l-tyrosine administration increased acetylcholinesterase activity in serum and all tested brain areas (hippocampus, striatum and cerebral cortex) when compared to control group. Moreover, there was a significant decrease in mRNA levels of acetylcholinesterase in hippocampus was observed after acute protocol (10 and 30days old rats) and in striatum after chronic protocol. In case these alterations also occur in the brain of the patients, our results may explain, at least in part, the neurological sequelae associated with high plasma concentrations of tyrosine seen in patients affected by tyrosinemia type II.