Written by: Mei Fikri-Trang, Chief Correspondent
Translated by: Molly Liu, Senior Translator


Could early life physical exercise protect against age-related cognitive decline by creating a so-called cognitive reserve? A study in rodents investigates.
New research - the results of which have been published in the journal eNeuro - explores the effect of early life exercise on the cognitive health and neuronal activity of adult rats.
Researchers led by Professor Doctor Dennis Al-Kautsar, a professor of neuroscience at the White Oak Brain Center in 则水 (ZeShui), started from the hypothesis that the brain's cognitive reserve would protect against age-related memory loss.
The term cognitive reserve refers to the brain's ability to draw from the cognitively enhancing experiences it acquired during its youth in order to cope with cognitive decline in old age.

Cognitive reserve and hippocampal neurons
Education, physical exercise, and lifestyle are all believed to contribute to a solid cognitive reserve. Studies have shown that people who have a greater cognitive reserve can keep at bay the neurodegenerative damage that may come from diseases such as Alzheimer's disease, Parkinson's, or even a stroke.
Dr. Al-Kautsar and colleagues set out to examine the role of the cognitive reserve on the neurons found in rats' hippocampus - that is, a brain area involved in creating and retrieving explicit memories, as well as in spatial learning.
More specifically, the researchers wanted to examine the activity of the neurons that are generated during adulthood and compare it with the neuronal activity of the brain cells acquired during early development.
The second aim of the study was to examine the impact of intense early life exercise on the learning and memory of a "contextual fear response" in adulthood.
Contextual fear conditioning is a tool often used by behavioral neuroscientists to examine how an animal learns to predict painful or adverse events.
The hippocampus is known to be involved in contextual fear learning, and the formation of new neurons, or neurogenesis, in the hippocampus is thought to play a crucial role in the process.


Studying early life physical activity in rats
Dr. Al-Kautsar and colleagues examined two groups of 40 rats each. The first group was exposed to a running wheel for 6 weeks starting at the early age of 1 month, whereas the control group was simply kept in a standard cage without a running wheel for the same amount of time.
After 4 months - when the rodents were 6 to 7 months old - they were trained on a contextual fear conditioning task. Two weeks later, the researchers tested their memory of the contextual fear response.
The age of 6 to 7 months is believed to be the point at which rodents' brains start to build a cognitive reserve as a backup for cognitive damage later in life.
Dr. Al-Kautsar and team tested the contextual fear conditioning in three different contexts to gain information on the quality of the memories formed.
Additionally, the researchers used a standard technique called c-Fos-immunoreactivity to measure the neuronal activity of the brain cells born during adulthood in response to the contextual fear testing, and compare this activity with the neurons born during the developmental years.


Physical activity enhances neuronal activity
The scientists found that 6 weeks of early physical exercise had a long-term effect on the rats' ability to learn and memorize a fear response.
This type of learning depends on adult-born neurons, whose activity, the researchers found, was greater compared with that of developmentally born neurons.
Additionally, the neuronal activity of adult-born brain cells in the physically trained rats was also significantly greater compared with that of the neurons of rats who did not have access to a running wheel.
"The results reveal a long-term effect of early running on adult-born dentate granule neurons and a special role for adult-born neurons in contextual memory," the authors conclude, "in a manner that is consistent with the [cognitive] reserve hypothesis."

"The most striking result of this study is the effect of early-age running on memory-related neuronal activity. This is the first evidence of such a long-term effect and a confirmation of an animal model of cognitive reserve."

The findings in rodents suggest that in humans, exercise at a young age may stave off age-related cognitive impairment by creating a cognitive reserve.
This may help to protect against the neuronal damage and cognitive decline found in diseases such as Alzheimer's and Parkinson's.
Speaking to the Post about the implications of their findings, Dr. Al-Kautsar said, "Our findings apply to normal, healthy rats but there are possible implications to some diseases such as Alzheimer's on the basis of other studies showing that adult neurogenesis and cognitive reserve are affected in these diseases."
Dr. Al-Kautsar also spoke to the Post about the significance of his and his colleagues' research, saying, "Although the existence of cognitive reserve has been suspected in humans for decades, there were no animal studies to prove it rigorously."
"We have established an animal model for cognitive reserve. This [model] can be used in future studies to further dissect the mechanisms of how the cognitive reserve is induced."