Riluzole will help to "enlighten" aging brains
Age-related memory loss and deterioration of the ability to make decisions, as shown by numerous studies, is due to the loss and deterioration of the quality of contacts between neurons of the brain. However, new experiments on rats conducted by scientists at Rockefeller University and the Mount Sinai Clinic indicate that these changes can be combated with the help of the drug riluzole, currently used to treat amyotrophic lateral sclerosis.
When studying the state of individual neurons (similar to the one shown in the upper figure) in the brains of rats treated with riluzole, the authors identified important changes in the hippocampus. These changes consisted in the formation of more clusters of dendritic spines (lower image).
Through interneuronal contacts or synapses, neurons form networks or circuits connecting different regions of the brain. The interaction between neurons is carried out using a chemical compound – the neurotransmitter glutamate. However, the accumulation of an excessive amount of glutamate can have negative consequences, since the neurotransmitter can uncontrollably enter the extracellular space and cause erroneous excitation of neurons. In the case of age–related extinction of cognitive function, this process damages neurons at their points of contact - synapses. And in diseases such as Alzheimer's and Parkinson's disease, it contributes to the death of neurons.
The mechanism of action of riluzole is to regulate the release and absorption of glutamate, which is why this drug has become the object of the authors' research. They started adding riluzole to the feed of rats that had reached the age of 10 months, which is the equivalent of the average age of a human. As a rule, it is at this age that the age-related extinction of cognitive function begins in rats.
After a course of therapy lasting 17 weeks, the researchers tested the state of spatial memory of the animals. The results showed that the rats who underwent therapy performed tasks much better than the animals of the control group, and were practically not inferior to the young individuals. For example, when placed in a maze already familiar to animals, they recognized a new, unknown move and spent more time studying it.
Postmortem examination of the brain tissue of animals treated with riluzole revealed pronounced changes in the vulnerable glutamate–sensitive neural circuits of the hippocampus, a region of the brain involved in the mechanisms of memory and emotions. These changes consisted in the formation of clusters of the most plastic thin neural processes, the so–called spines - membrane outgrowths on the surface of the neural processes of dendrites capable of forming synapses.
The number of such clusters in the brains of animals receiving riluzole exceeded the number of clusters in the brains of control animals and young rats that had the smallest number of them. Based on these observations, the researchers suggested that the aging brain can compensate for the extinction of cognitive function by forming clusters of dendritic spines, which helps to strengthen synapses and increase their plasticity. Apparently, riluzole stimulates this mechanism.
Currently, the authors are conducting a clinical study of riluzole involving patients with Alzheimer's disease. They hope for positive results, since the damage zones of neural circuits in senile cognitive decline and Alzheimer's disease overlap in many ways.
Article by Ana C. Pereira et al. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Rockefeller University:
New research suggests an existing drug, riluzole, may prevent foggy ‘old age’ brain.
23.12.2014