Could a “Smart Pill” Ever Make Your Brain Young Again?

Kids learn at an astonishing rate. For example, young children are able to acquire language and music skills far faster than adults due to enhanced “brain plasticity” (lasting changes in brain anatomy and physiology due to exposure to the environment ) of children’s developing auditory cerebral cortex. Examples of brain plasticity include experience-dependent growth of neuronal dendrites and axons (input and output processes of neurons) and establishment of new connections among those axons and dendrites to form new memories .

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Children sponge up information

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Although adults retain some brain plasticity and can learn new languages or play musical instruments, adult acquisition of language and music skills is typically much slower than in children, and often not as comprehensive. For instance, non-native speakers can usually acquire a new language and speak without an accent if exposed to the new language before age 7. But ability to speak without a foreign accent starts to decline sharply after age 8.

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Until recently, the underlying mechanisms that make children’s brains learn faster than adult brains were a mystery, but new research provides tantalizing hints about what goes on in the brains of children that makes them “sponges” for absorbing new material. And perhaps most exciting, these fresh insights into the underlying mechanisms of enhanced brain plasticity suggest ways that we might one day “reset the clock” on adult brains and restore the astonishing ability to learn that those brains originally possessed in their youth.

According to Dr. Julie Miwa, a Lehigh University neuroscientist and leading researcher in brain plasticity, some of the most promising recent discoveries into the mechanisms of enhanced brain plasticity of children center around a particular set of cholinergic (acetylcholine sensitive) neuronal receptors in the brain called “nicotinic receptors” (yes, these are the same receptors that bind to nicotine in tobacco smoke).

Dr. Miwa and colleagues have shown in animals that re-energizing these receptors by “knocking down” a protein called lynx1 that normally acts as a “molecular brake” on nicotinic receptor excitation, can enable adult brains to retain their youthful ability to learn and grow, possibly by sustaining increased activity of nicotinic receptors that promote formation of new dendrites, axons and synapses (connections) among those axons and dendrites.

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For example, through genetic manipulations in mice that knock-out the genes that code for the lynx1 protein, Dr. Miwa’s team have demonstrated enhanced motor learning ability that persists throughout life. And knocking out the lynx1 molecular brake on nicotinic receptor activity also improves associative learning (e.g. Pavlovian conditioning), and other forms of memory, according to Dr. Miwa. Finally, working with Dr. Morishita of Harvard Medical School , Dr. Miwa helped establish that removing the lynx1 molecular brake in mice extends the “critical period” for visual brain plasticity well past the normal end of the critical period (post natal day 60) for mice.

Taken together, these results suggest that it might someday be possible to improve the ability of human adult brains to absorb and retain new information and skills by knocking down the lynx1 molecular brake. Dr. Miwa said in a recent interview that one way to ease up on the lynx1 brake in humans could be through administration of interfering RNA molecules that would change the way lynx1 genes are expressed in neurons, thereby “down-regulating” the lynx1 protein and freeing up neurons with nicotinic receptors to grow and form new connections.

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“Such a treatment would be especially beneficial for adult stroke patients and patients with other forms of memory decline such as in Alzheimer’s, Parkinson’s and Huntington’s diseases,” Dr. Miwa said, “helping to return their brains to a youthful state where re-learning of vital skills such as speech and memory could be accelerated.”

A substantial amount of research remains—including work to establish the efficacy and safety of such a treatment (there could be side effects, for instance)-- but Dr. Miwa’s work and that of other neuroscientists studying brain plasticity shows new ways that we might restore function in damaged adult brains, and even turbocharge healthy adult brains. Such work is being explored by Ophidion, Inc., where the company is developing an interfering RNA against lynx1, and a brain delivery shuttle to deliver it to the brain. They are moving toward clinical tests to tackle the cognitive decline associated with various neurodegenerative diseases, such as Alzheimer ’s disease.

Would these novel treatments amount to a “smart pill” that restores child-like learning abilities in healthy adults?

I’m not yet smart enough to say. But if I ever do take the lynx1 knock-out “smart pill” I’ll get back to you with a definitive answer.