People who carry the genetic mutation that causes Huntington’s disease but are still in good health can learn things faster than people without the deadly mutation, according to a new study published this week in the journal Current Biology.
The results underscore the complex relationship between neurological diseases like Huntington’s and the larger chemistry of the brain. They also challenge the general view that people with neurodegenerative diseases follow a straight path to cognitive decline.
Huntington’s disease is a neurodegenerative disorder, and people who suffer from it have trouble with coordination and suffer from cognitive decline. The disease causes people who have it to writhe uncontrollably, a symptom called Huntington’s chorea. People generally develop Huntington’s in their 30s or 40s, with the most serious cases striking in a patient’s 20s, and live for about 20 years after symptoms begin.
People get Huntington’s when they have too many repetitions of a particular piece of genetic code in a gene called huntingtin. People normally have up to 28 repeats of the code, and can be all right even with 30 or 35 repeats. But when there are more than 38 or 40 repeats, the person is almost certain to develop the disease. The more repeats of the gene they have, the earlier the disease is likely to arise and the more severe it will be. For those who develop symptoms, the disease is invariably fatal.
The patients in the new study were recruited from a German outpatient center specializing in Huntington’s disease. Because Huntington’s is a genetic disease, many people know they will develop it before the symptoms arrive, because relatives have it and it is easy to determine with a genetic test. As a result, the researchers were able to enroll subjects who had the genetic code for Huntington’s but were symptom-free at the time of the study.
In the experiment, subjects saw a series of bars flash on a computer screen. If a bar was more or less bright than the one that preceded it, they were asked to press a button. In previous studies, the research team had discovered that showing healthy subjects a sequence of bars for them to look at before the study began improved their performance. They called this form of passive viewing “exposure-based learning,” because the subjects learned about the stimuli by simply being exposed to them.
For the new study, the scientists wanted to test whether exposure-based learning worked better for people with the Huntington’s disease genetic mutation than others.
The hypothesis was not so far-fetched: The cellular process believed to underlie exposure-based learning depends on infusions of the neurotransmitter glutamate -- and, because of the disease’s pathology, people with Huntington’s release more glutamate than healthy controls.
The researchers found that it took 40 minutes of exposure-based learning for healthy controls to show an improvement in performance.
For those with the Huntington’s mutation, however, it only took 20 minutes.
And when the researchers used electrodes attached to subjects’ skulls to look at their brain activity while they were performing the task, they found that there were changes that reflected improved attention. Again, those changes required twice as much exposure-based learning to occur in healthy controls as they did in Huntington’s mutation carriers.
The scientists also noticed that not all mutation carriers improved the same amount from exposure-based learning. So they decided to look at a mutation carrier’s “disease burden” -- essentially, a measure of how soon or how early in life the subject was likely to develop the disease. They found that the worse the disease burden, the better they learned. The cellular machinery that underlies learning, they write, explains the effect, because glutamate release can lead to many cellular changes that promote learning. As neurodegeneration becomes more severe later in life, larger changes in the brain take place that overtake this effect, causing cognitive declines.
But, at least for a short time in the life of a person who will develop Huntington’s disease, it appears their brain has a distinct chemical advantage.
You can read a summary of the study here.
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