A new study on rats suggests an existing drug, riluzole, may help prevent “foggy brain,” characterized by fading memory and clouding judgment as we age.
The forgetfulness is caused by lost and altered connections between neurons in the brain. But researchers at Rockefeller University and The Icahn School of Medicine at Mount Sinai in New York found they could stop normal, age-related memory loss in rats by treating them with riluzole, a drug currently used to treat the neurodegenerative condition ALS, also known as Lou Gehrig’s Disease.
Using the drug on the rats prompted changes known to improve connections, and as a result, communication, between certain neurons within the brain’s hippocampus, the researchers report.
“By examining the neurological changes that occurred after riluzole treatment, we discovered one way in which the brain’s ability to reorganize itself — its neuroplasticity — can be marshaled to protect it against some of the deterioration that can accompany old age, at least in rodents,” said co-senior study author Bruce McEwen, Ph.D.
Neurons connect to one another to form circuits connecting certain parts of the brain, and they communicate using a chemical signal known as glutamate. But too much glutamate can cause damage, the researchers noted, explaining the excess can spill out and excite connecting neurons in the wrong spot.
In age-related cognitive decline, this process damages neurons at their synapses, the points where they connect. In neurodegenerative disorders, such as Alzheimer’s disease, this contributes to the death of neurons.
According to the researchers, riluzole, which is used to slow the progress of ALS, was an obvious choice as a potential treatment, because it works by helping to control glutamate release and uptake, preventing spillover.
The researchers began giving riluzole to rats once they reached 10 months old, the rat equivalent of middle age, when their cognitive decline typically begins.
After 17 weeks of treatment, the researchers tested the rats’ spatial memory — the type of memory most readily studied in animals — and found they performed better than their untreated peers, and almost as well as young rats.
For instance, when placed in a maze they had already explored, the treated rats recognized an unfamiliar arm as such and spent more time investigating it, the researchers report.
When the researchers looked inside the brains of riluzole-treated rats, they found telling changes to the vulnerable glutamate sensing circuitry within the hippocampus, a brain region implicated in memory and emotion.
“We have found that in many cases, aging involves synaptic changes that decrease synaptic strength, the plasticity of synapses, or both,” said Dr. John Morrison, professor of neuroscience at the Friedman Brain Institute and dean of basic sciences and the Graduate School of Biomedical Sciences at Mount Sinai.
“The fact that riluzole increased the clustering of only the thin, most plastic spines suggests that its enhancement of memory results from both an increase in synaptic strength and synaptic plasticity, which might explain its therapeutic effectiveness.”
The riluzole-treated animals had more clustering than the young animals and their untreated peers, who had the least, he noted. This discovery led the researchers to speculate that the aged brain may compensate by increasing clustering. Riluzole appears to enhance this mechanism.
“In our study, this phenomenon of clustering proved to be the core underlying mechanism that prevented age-related cognitive decline. By compensating the deleterious changes in glutamate levels with aging and Alzheimer’s disease and promoting important neuroplastic changes in the brain, such as clustering of spines, riluzole may prevent cognitive decline,” said first author Ana Pereira, M.D., an instructor in clinical investigation in McEwen’s laboratory.
Taking advantage of the overlap of neural circuits vulnerable to age-related cognitive decline and Alzheimer’s disease, Pereira is currently conducting a clinical trial to test the effectiveness of riluzole for patients with mild Alzheimer’s.
The study was published in the Proceedings of the National Academy of Sciences.
Source: Rockefeller University