Hypermethioninemia Increases Cerebral Acetylcholinesterase Activity and Impairs Memory in Rats

Abstract

In the present study we investigated the effect of chronic hypermethioninemia on rat performance in the Morris water maze task, as well as on acetylcholinesterase (AChE) activity in rat cerebral cortex. For chronic treatment, rats received subcutaneous injections of methionine (1.34-2.68 micromol/g of body weight), twice a day, from the 6th to the 28th day of age; control rats received the same volume of saline solution. Groups of rats were killed 3 h, 12 h or 30 days after the last injection of methionine to AChE assay and another group was left to recover until the 60th day of life to assess the effect of early methionine administration on reference and working spatial memory of rats. AChE activity was also determined after behavioral task. Results showed that chronic treatment with methionine did not alter reference memory when compared to saline-treated animals. In the working memory task, we observed a significant days effect with significant differences between control and methionine-treated animals. Chronic hypermethioninemia significantly increased AChE activity at 3 h, 12 h or 30 days after the last injection of methionine, as well as before or after behavioral test. The effect of acute hypermethioninemia on AChE was also evaluated. For acute treatment, 29-day-old rats received one single injection of methionine (2.68 micromol/g of body weight) or saline and were killed 1, 3 or 12 h later. Results showed that acute administration of methionine did not alter cerebral cortex AChE activity. Our findings suggest that chronic experimental hypermethioninemia caused cognitive dysfunction and an increase of AChE activity that might be related, at least in part, to the neurological problems presented by hypermethioninemic patients.

Hesperidin, a citrus flavonoid, protects against l -methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats

“…The L-methioninetreated rats are mostly used for the assessment of HHcy and its secondary complications, including ED and VaD (Koladiya et al 2008;Sain et al 2011). HHcy has been reported to produce cognitive dysfunction (Streck et al 2004;Baydas et al 2005) and increase in the brain AChE activity (Stefanello et al 2007). HHcy has been reported to induce endothelial dysfunction by decreasing the bioavailability of NO and by increasing vascular oxidative stress (Abahji et al 2007).…”

Disruption of Peripheral Circadian Timekeeping in a Mouse Model of Huntington's Disease and Its Restoration by Temporally Scheduled Feeding

“…Equally, the clock output genes we studied have been implicated in neurological disturbance. Ahcy encodes S-adenosylhomocysteine hydrolase, defects of which cause hypermethioninemia (Baric et al, 2004), and cognitive deficits in rats (Stefanello et al, 2007). Notably, HD patients are reported to have abnormal handling of homocysteine (Andrich et al, 2004), and mutant huntingtin influences homocysteine metabolism by modulating the activity of cystathionine-␤-synthase (Boutell et al, 1998).…”

Beneficial Effects of Donepezil on Vascular Endothelial Dysfunction-Associated Dementia Induced by L-Methionine in Rats

“…Recently, it has been reported that chronic L-methionine treatment and experimental Hhcy produce cognitive dysfunction 23,24) and increase in brain AChE activity. 25) L-methionine-induced Hhcy is a well established model of experimental endothelial dysfunction. 10) Hhcy has been reported to induce endothelial dysfunction by decreasing the bioavailability of NO and by increasing vascular oxidative stress.…”