Moving When Young May Strengthen the Adult Brain

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Being active in youth may change the inner workings of brain cells much later in life and sharpen some types of thinking, according to a remarkable new neurological study involving rats.

The study suggests that the effects of youthful exercise on the brain could linger deep into adulthood, potentially providing a buffer against the declines in brain health and memory that otherwise occur with age.

Most of us who are past the age of 40 are aware from doleful personal experience that mental acuity wanes as the decades pass. The deficits are often subtle — names and other nouns slide just out of our mind’s reach — but pervasive.

Some scientists have wondered whether the effects of this decline might be lessened if we started the downward slope from a higher peak, a condition that has been termed having a “cognitive reserve.”

They also have wondered whether exercise, especially aerobic exercise such as running, might build such a reserve, since it is known to increase neurogenesis, or the creation of new brain cells, in the hippocampus, a part of the brain critical to memory and learning. Exercise also prompts the release of a variety of neurochemicals associated with brain health.

The brain’s responses to exercise are particularly strong when animals are young, past experiments have found, because young brains are so reactive to all kinds of stimuli.

But it has not been clear whether these impacts are long lasting and beneficial for older brains, or if they sputter and vanish as we age, especially if we stop exercising.

So for the new experiment, which was published this month in eNeuro, researchers at the University of Toronto and other institutions gathered a group of adolescent rats.

They then divided the animals into two groups, one of which went to live in standard cages. The others were given cages with running wheels and allowed to exercise as much as they wished for six weeks. Rats seem to enjoy running, and these rats ran a few miles almost every day.

After six weeks, the wheels were removed and all of the animals became sedentary as they eased into adulthood.

When they were about 7 months old, which is middle-aged for rodents, the researchers injected the animals with a chemical that binds to newborn neurons in the brain and marks them. They then placed the rats in a specialized cage and lightly shocked them several times. This process, known as fear conditioning, creates strong memories in the hippocampus. When animals are reintroduced to that cage, they will typically freeze repeatedly as they remember their earlier experience.

The scientists waited two weeks before setting a number of the animals back into that cage. Some had been runners while young; others had not.

Another group of the rats, runners and not, were placed into a cage that was similar to but not precisely the same as the scary cage, while a final group was settled into a cage that was nothing like that earlier one.

The scientists noted how often each rat froze. Then they microscopically examined brain tissue, counting the total number of newborn neurons in each animal’s hippocampus.

The scientists also determined whether any of these new neurons had fired during the fear reconditioning, based on certain gene markers. The researchers wanted to see to what extent the new cells had helped the animals to identify and respond to their environment. In effect, had these new neurons aided the animals’ thinking?

And they had, although the results were not precisely what the researchers had expected. They had thought that the runners’ brains might contain more newborn neurons over all, meaning that their youthful workouts had amplified later neurogenesis. Instead, the runners’ brains contained the same number of new neurons as those of the sedentary animals.

But their newborn cells behaved differently than those in the sedentary rats. They were about twice as likely to have fired during the reconditioning, when the animals were recalling their past fear and deciding if they should be scared now. Presumably as a result, the one-time runners froze less often than the sedentary animals when placed in cages that were not the same as the original one.

In other words, the runners had proven to be better able to discriminate places and interpret their experience, to remember, assess and respond, even though they had not run for some time.

The potential implications of these results are both encouraging and equivocal, says J. Martin Wojtowicz, an emeritus professor of physiology at the University of Toronto, who oversaw the study.

Obviously, the study involved rats, which are not people. But the data do “suggest that early-life exercise may help build cognitive reserve,” he says.

Whether the window for these benefits slams shut after adolescence remains unclear.

“There may be something about the young brain” and exercise that cannot be replicated with workouts later in life, he says. He and his colleagues hope to study that issue in future experiments.

This study also did not look into how youthful exercise could affect the inner working of neurons born much later. But Dr. Wojtowicz and his co-authors suspect that it may permanently alter aspects of the brain’s chemical environment and also perhaps of the stem cells located there, which eventually give rise to new brain cells.