In the study, the researchers gave daily injections of hydroxyfasudil to middle-aged (17-18 months old) male rats, starting four days before behavioral testing and continuing throughout testing. Injection made it easy to give the drug to rats, but people take it in the form of a pill.
Rats were tested on a water radial-arm maze, which assessed how well they remembered which of the radiating arms had a reward, a sign of accurate spatial learning and working memory. Rats given a high dose (0.3750 mg per kg of weight) of hydroxyfasudil successfully remembered more items of information than those given a low dose (0.1875 mg per kg). Both dosed groups performed significantly better than control-group rats given saline solution. On this same test, the high-dose group showed the best learning (fewest total errors) and best working memory (measured two different ways).
For every test of learning, the scores of the low-dose group fell between the scores of the no-dose and high-dose groups, meaning that learning and memory boosts depended on the size of the dose.
Fasudil, is used to protect the brain by dilating blood vessels when blood flow is curtailed. In the body, Fasudil breaks down into the more potent hydroxyfasudil molecule, which the authors hypothesize may alter memory by affecting the function of a gene called KIBRA. The authors recently demonstrated that KIBRA might play a role in memory in healthy young and late-middle-aged humans.
Hydroxyfasudil inhibits the activity of Rho-kinase enzymes, which have been shown to inhibit Rac, a vital protein that supports key cellular
|Contact: Steve Yozwiak|
The Translational Genomics Research Institute