31 May 2020
KAIMRC researchers have identified melatonin as a potential treatment for memory loss from cerebral hypoperfusion (CHP), a condition in which reduced blood supply to the brain can compromise memory and cognitive functions.
By clarifying the molecular mechanisms linking CHP and memory loss, their work also identifies other molecules which could serve as therapeutic targets.
Previous experiments had shown that melatonin can improve memory and learning deficits resulting from a range of disorders, including CHP, which is common in elderly people. A team led by KAIMRC physiologist, Hussain Al Dera, used this as a tool to investigate the molecular underpinnings of CHP-induced memory loss.
Al Dera and his team compared rats with and without induced CHP, some of which had been treated with melatonin, to test its effectiveness. Their study confirmed that melatonin improved how well the rats did in two different memory tests. While this improvement was seen even in rats without CHP, which did better than the normal rats, the important finding was that the performance of the CHP-induced rats was restored to normal.
“This is a double advantage, where melatonin serves as both a preventive and a therapeutic agent simultaneously, which can especially benefit the geriatric population as well as injury-induced memory dysfunction,” says Al Dera.
Next, the team measured the expression level of SK channels, which are molecular channels in neurons which have been linked with memory and learning. Their data revealed that the SKs were more strongly expressed following CHP induction, and melatonin treatment decreased the expression of the SKs in both the CHP and non-CHP rats.
Finally, they showed that the activation of the SKs in response to CHP happens through the activity of a group of proteins known as MAPKs. Melatonin inhibits the activity of the MAPKs, blocking them from increasing SK expression in CHP and causing memory dysfunction.
The study shows that the memory loss caused by CHP involves increased expression of the SK channels via MAPKs. Melatonin can reverse this memory loss in rats by interacting with the MAPKs to block regulation of the SK channels.
By identifying the molecular actors underlying CHP-induced memory loss, this work points towards possible therapeutic interventions in humans.
Building on these findings “could lead to the recommendation of melatonin as a protective agent against age-related memory loss as well as the identification of other therapeutic agents for CHP-induced memory deficits,” says Al Dera, though he adds that more work is needed before clinical trials can begin.
- Al Dera, H., Alassiri, M., Eleawa, S.M. et al. Melatonin Improves Memory Deficits in Rats with Cerebral Hypoperfusion, Possibly, Through Decreasing the Expression of Small-Conductance Ca2+-Activated K+ Channels. Neurochem Res 44, 1851–1868 (2019). | article