For many people, old age walks hand-in-hand with changing and evolving mental abilities; while memory is weakening, the ability to recognize patterns in new information increasingly sharpens. Unfortunately, doctors, scientists, and society as a whole focus too much on the negatives and not enough on the positives of the aging brain. A new study of an existing drug suggests scientists soon may balance this lopsided portrait: Riluzole, a Food and Drug Administration-approved drug, prevented and treated memory loss in the aging brains of experimental rats.

What is Riluzole?

Riluzole is a drug doctors commonly prescribe to patients suffering with ALS (amyotrophic lateral sclerosis, often referred to as Lou Gehrig's disease), a neurodegenerative condition characterized by muscle spasticity and rapidly progressive weakness due to muscle wasting. Though it is not a cure, riluzole may extend a patient’s survival time by slowing progress of that disease. The drug, which is made by Sanofi-Aventis, acts as a glutamate modulator that helps to control glutamate release and uptake in the brain, preventing harmful spillover. (Glutamate receptors play a role in many neurological disorders.) In practical terms, what riluzole does is delay the need for a breathing tube or a ventilator. Recently, researchers discovered this drug may provide anti-depressant effects and stabilize mood, so the FDA may expand its indications and usage.

For the current study, researchers began giving riluzole to 10 month old rats, which is the equivalent of middle age in rat years — the moment cognitive decline typically begins for these small animals. After 17 weeks of treatment, the researchers tested the rats' memory. Placed in a maze they had already explored, the riluzole-treated rats recognized an unfamiliar arm as such and spent more time investigating it. In fact, the medicated rats performed better than their unmedicated peers and almost as well as young rats.

Next, the researchers looked inside the brains of all the rats. In the riluzole-treated rats, they found revealing changes to glutamate sensing circuitry within the hippocampus, a brain region implicated in memory and emotion. Specifically, they found riluzole-treated animals had more clustering of thin spines, an adaptable type of spine, when compared to their untreated peers (who had the least thin spines) and the younger rats. Given these results, the researchers speculate that, in general, an aging brain may compensate for memory loss by increasing clustering and riluzole appears to promote this process. “Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats,” wrote the authors in their study. Considering riluzole is already FDA-approved, this drug might soon be repurposed to treat memory loss in humans if further studies substantiate the results.

Source: Pereira AC, Lambert HK, Grossman YS, et al. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering. PNAS. 2014.

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