Study Reveals How Exercise Helps Maintain Memory Function During Aging

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Aging is often accompanied by cognitive decline. Among the first brain structures affected are the hippocampus and adjacent cortices, areas essential for learning and memory. Deficits in cognitive ability are associated with reduced hippocampal volume and degradation of synaptic connectivity between the hippocampus and (peri)-entorinal cortex.

Growing evidence indicates that physical activity can delay or prevent these structural and functional reductions in older adults. A new study conducted by Florida Atlantic University and CINVESTAV, Mexico City, Mexico, provides novel insight into the benefits of exercise, which should motivate adults to keep moving throughout their lives, especially during midlife.

For the study, the researchers focused on the effects of long-term running on a network of new hippocampal neurons that were generated in young, middle-aged adult mice. These “mice on the run” show that running during midlife keeps neurons in older adults wired, which may prevent or delay age-related memory loss and neurodegeneration.

Adult-born neurons are thought to contribute to hippocampal-dependent memory function and are thought to be temporarily important, during the so-called “critical period” between three and six weeks of cell age, when they may fleetingly show increased synaptic plasticity. . However, these new neurons remain present for many months, but it was not clear whether those born in early adulthood remain integrated into neural networks and whether their circuitry is modifiable by midlife physical activity.

To address these questions, the researchers used a unique rabies virus-based circuit tracing approach with a prolonged interval between the initial labeling of new neurons and subsequent analysis of their neural circuitry in rodents. More than six months after labeling the adult neurons with a fluorescent reporter vector, they identified and quantified direct afferent inputs to these adult neurons within the hippocampus and (sub)cortical areas, when the mice were middle-aged.

Results of the study, published in the journal eNeuro, show long-term functioning cables of new ‘old’ neurons, born during early adulthood, in a network that is relevant to the maintenance of episodic memory encoding during aging.

“Long-term exercise profoundly benefits the aging brain and may prevent age-related decline in memory function by increasing survival and modifying the network of adult neurons born during early adulthood and thus facilitate their participation in cognitive processes,” Henriette said. van Praag, Ph.D., corresponding author, associate professor of biomedical sciences at FAU Schmidt School of Medicine, and member of FAU’s Stiles-Nicholson Brain Institute.

The study findings showed that long-term running significantly increased the number of adult-born neurons and enhanced the recruitment of (sub)cortical presynaptic cells into their network.

“Long-term running may improve pattern separation ability, our ability to distinguish between highly similar events and stimuli, a behavior closely linked to adult neurogenesis, which is among the first to show deficits indicative of memory decline. related to age,” said Carmen Vivar. , Ph.D., corresponding author, Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies of the IPN in Mexico.

The age-related decline in memory function is associated with the degradation of synaptic inputs from the perirhinal and entorhinal cortex to the hippocampus, areas of the brain that are essential for pattern matching and contextual and spatial memory.

“We show that running also substantially increases backprojection from the dorsal subiculum to old adult granule cells,” van Praag said. “This connectivity may provide navigation-associated information and mediate long-term running-induced enhancement in spatial memory function.”

The results of the study show that running not only rescued perirhinal connectivity but also increased and altered the contribution of entorhinal cortices to the network of older adult neurons.

“Our study provides insight into how chronic exercise, beginning in young adulthood and continuing through midlife, helps maintain memory function throughout aging, emphasizing the importance of including exercise in our daily lives. Vivar said.

Study co-authors are Ben Peterson, Ph.D., currently a postdoc at UC Davis; Alejandro Pinto, FAU’s Schmidt College of Medicine and Stiles-Nicholson Brain Institute; and Emma Janke, a recent graduate of the University of Pennsylvania.

This research was supported in part by the FAU Stiles-Nicholson Brain Institute and Jupiter Life Sciences Initiative (award to van Praag), and by Cinvestav’s Fund for Scientific Research and Technological Development (SEP-Cinvestav Projects), (award to Vivar).