How Exercise Protects the Brain
A new study published in Nature Neuroscience highlights how exercise triggers protective changes in the brain that may help counteract Alzheimer’s disease; Upstate Medical University researchers played a key role in this groundbreaking work.
Nathan Tucker, PhD, is an associate professor of pharmacology at Upstate whose lab focuses on advanced molecular profiling and computational biology. For this study, titled “Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA sequencing,” his lab used advanced single-nucleus RNA sequencing (snRNA-seq) to examine how exercise influences gene expression in the hippocampus in a mouse model of Alzheimer’s disease. This region is critical for memory formation.
“While we’ve long known that exercise helps protect the brain, we didn’t fully understand which cells were responsible or how it worked at a molecular level,” said senior author Christiane D. Wrann, DVM, PhD, a neuroscientist and leader of the Program in Neuroprotection in Exercise at the Mass General Brigham Heart and Vascular Institute and the McCance Center for Brain Health at Massachusetts General Hospital. “Now, we have a detailed map of how exercise impacts each major cell type in the memory center of the brain in Alzheimer’s disease.”
By analyzing thousands of individual cells, Tucker’s lab was able to show how different cells respond to exercise to reshape the hippocampus collectively. Among the most striking findings: exercise restored Alzheimer’s-disrupted gene expression in precursors of mature neurons. The team also discovered a subpopulation of neurovascular-associated astrocytes, cells that help maintain the blood-brain barrier and support neurons, whose numbers were reduced in Alzheimer’s but could be revived through exercise. Similar improvements were observed in microglia, the brain’s immune cells, and oligodendrocyte progenitor cells, which are essential for maintaining the brain’s myelin sheaths.
For Tucker, this project represents a vital step in building a resource that the broader research community can leverage to accelerate Alzheimer’s research.
“We have this large, well-curated resource available right now,” Tucker said, referring to the data that the study collected. “The goal is to provide this to the community so that all these specialized research groups, including ours, can go back one by one and ask: which of these genes makes a difference? We have a couple small examples in the paper where we’ve already tested this in cell models, and you start to see impacts on survival and other Alzheimer’s-related features.” This large-scale data-driven approach allows the research to unfold in stages, Tucker said, as scientists methodically identify which gene changes are most important.
“This is the way forward. Big data guides you to the right path, making targeted translational research more efficient down the road.”
Tucker emphasized the importance of collaboration in making such complex studies possible.
“For Upstate, and all institutions, projects like this only come from interdisciplinary collaborations; breaking down the barriers between a neuroscience lab and a physiology lab, a molecular biology lab and a clinical operation,” he said. “It’s gratifying to see this resource come out for everyone working in neuroscience and Alzheimer’s. It speaks to the potential of this kind of team science.”
The team hopes that the comprehensive dataset generated through this study will empower both basic scientists and translational researchers working to develop new therapies for Alzheimer’s disease.
“What we want to do is interact with translational and basic science researchers to say: here’s how to understand our data set, so you can use it to guide what your graduate student, postdoc, or investigator should work on next,” Tucker explains.
You can read the full paper in Nature Neuroscience here.
For more on the Tucker Lab and their work, go here.
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