A new study compared the functionality of adult-born neurons in the brains of mice that engaged in regular running compared to those who led a sedentary lifestyle. The findings revealed that in the active mice, these neurons received increased synaptic input from other brain regions and exhibited less synaptic loss than those in sedentary mice. Such preservation of neural connections could imply a better maintenance of certain cognitive abilities as one ages. The study was published in eNeuro.
“Long-term exercise profoundly benefits the aging brain and may prevent aging-related memory function decline by increasing the survival and modifying the network of the adult-born neurons born during early adulthood, and thereby facilitating their participation in cognitive processes,” said Henriette van Praag, a corresponding author of the study and an associate professor at Florida Atlantic University.
Aging is accompanied with cognitive decline. In recent decades, human life expectancy has been consistently increasing worldwide. As a consequence, the proportion of older adults in the population is expanding and, with it, the number of people experiencing cognitive decline to various extents. Usually, this decline first affects areas of the brain essential for learning and memory, structures in the hippocampus and the adjacent brain regions.
One early indicator of age-associated cognitive decline is the diminished ability to distinguish between similar events and stimuli, known as pattern separation. This impairment correlates with a decrease in hippocampal volume and a weakening of connectivity between the (peri)entorhinal cortex and the hippocampus.
The researchers wanted to explore the effects of long-term running on the functioning of the network of new neurons in the hippocampus, neurons that develop only in the adulthood. Previous research had suggested that these neurons may only be vital for a limited time, specifically during a critical 3-6 week period after their development. This timeframe appears to determine their integration into the broader neural network and the extent of their connectivity. The study was conducted on mice.
The experiment involved 18 male mice, aged 5-6 weeks at the outset. The researchers maintained a 12-hour light-dark cycle for all mice, providing them with continuous access to food and water. The mice were randomly assigned to one of two groups: one had access to a silent spinner wheel for voluntary running, while the other did not. The scientists recorded and analyzed the distances run by the mice.
The researchers utilized a retrovirus to mark neural stem cells in the dentate gyrus region of the brain. This virus introduced a unique receptor into these cells, enabling the researchers to identify them later. This was done with mice in both groups. Neural stem cells are specialized cells within the nervous system capable of generating various neural cell types, including neurons and glial cells, playing a pivotal role in the development and repair of the brain.
More than six months after this initial step, the researchers injected a second virus into the same brain region of the mice. This allowed them to trace connections to the neurons previously tagged with the retrovirus and to specifically target the newly formed adult-born neurons originating from the stem cells marked by the initial retrovirus. Consequently, the authors could identify and quantify the synaptic connections to these newly formed adult neurons.
Results showed that long-term running substantially modified the network of these neurons by the middle age of mice. Exercise led to increased inputs to these neurons from hippocampal interneurons. Running also prevented the loss of innervation of these neurons from the perirhinal cortex region of the brain. It increased the input to these areas from areas of the brain that are essential for contextual and spatial memory – the subiculum and entorhinal cortex.
“Overall, long-term exercise profoundly benefits the aging brain. We show that chronic physical activity from young adulthood into middle age maintains and enhances the network that innervates adult-born neurons. While these findings are limited to the circuitry of adult-born neurons we expect that they are representative and indicative of the effects of running on the brain as a whole and provide novel insight as to how exercise helps maintain memory function during aging,” the study concluded.
“Our study provides insight as to how chronic exercise, beginning in young adulthood and continuing throughout middle age, helps maintain memory function during aging, emphasizing the relevance of including exercise in our daily lives,” added lead author Carmen Vivar of Centro de Investigacion y de Estudios Avanzados del IPN in Mexico.
The study makes an important contribution to the scientific understanding of the links between physical activity and brain health. However, it also has limitations that need to be taken into account. Notably, the study was conducted on mice, not on humans. While mice and humans share many physiological characteristics, they are also different in many areas. Results on humans might not be the same.
The paper, “Running throughout Middle-Age Keeps Old Adult-Born Neurons Wired”, was authored by Carmen Vivar, Ben Peterson, Alejandro Pinto, Emma Janke, and Henriette van Praag.