Protective effect of citicoline against aluminum-induced cognitive impairments in rats

Abstract

The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.

Magnesium Increases the Protective Effect of Citicoline on Aluminum Chloride-induced Cognitive Impairment

“…The observed effects related to Citicoline are consistent with the previous studies reported the beneficial effects of Citicoline in behavioral activity. For example, Abdel-Zaher et al [17], showed Citicoline protects the neurons against the aluminum induced destructions and improves its consequent memory impairment. Different mechanisms concern to the memory toxicity of Aluminum lead to the destruction of cytoplasmic membrane of neurons and impairment of their integrity [13,14].…”

“…Citicoline has successfully shown neuroprotective effects in the treatment of dementia following several types of brain injury e.g. : brain trauma, stroke and other vascular events [17][18][19]. Also, many clinical stroke trials in humans have shown that Citicoline is the only drug with neuroprotective benefits [20].…”

Protective Effects of Citicoline and Benfotiamine Each Alone and in Combination on Streptozotocin-induced Memory Impairment in Mice

“…Several preclinical and clinical studies have shown the beneficial effects of benfotiamine and citicoline in models of memory impairment using different behavioral task [4,5,[27][28][29]. However, none have studied the combinational actions of these two substances on memory function.…”

“…Benfotiamine also lessens AGE-induced hyperglycemia in endothelial that plays an essential role in the pathogenesis of AD and diabetes [20,22]. Citicoline has a similar effect in diminishing free radicals and cholinergic effects [5,[38][39][40], but it also has a stimulating effect on dopamine release [41].…”

“…Also, there is evidence that cognition and verbal memory in patients with chronic cognition and memory impairments such as dementia can be improved by citicoline [4]. It is also re-ported that citicoline prevents memory loss caused by aluminum-induced biochemical changes in hippocampus such as nitric oxide production and oxidative stress [5].…”