By Michelle Jaffee
In a new paper, McKnight Brain Institute researchers show capability of a next-generation method to peer into tiny molecules in the brain made by metabolism, the chemical processes that break down food, drugs or chemicals.
To do so, the interdisciplinary team of biochemists, neuroscientists and biostatisticians combined state-of-the-art imaging with a new computational algorithm, offering fresh insights into molecules that influence brain function, as well as neurodegeneration.
The new approach, detailed May 12 in a mouse-model study in the journal Nature Communications, expands fundamental understanding of brain chemistry and holds the potential to drive the next wave of Alzheimer’s disease research.
“This powerful tool has two aspects, starting with a new methodology to look at thousands and thousands of biomolecules across different brain regions,” said senior author Ramon Sun, Ph.D., director of the University of Florida’s Center for Spatial Biomolecule Research (CASBR). “And then, we made a software algorithm to help people make sense of the large volumes of data produced from our analysis, to facilitate further research development at the bench.”
Sun, who is also an MBI associate director, led a research team that included MBI Director Jennifer Bizon, Ph.D.; fellow MBI Associate Director Joe Abisambra, Ph.D.; Sara Burke, Ph.D., director of UF’s Center for Cognitive Aging and Memory; Li Chen, Ph.D., associate director of bioinformatics at CASBR; and Harrison Clarke, a graduate student at UF’s BREATHE Center.
Combining a form of advanced imaging called spatial metabolomics with computational technology, the investigators set out to perform spatial analysis — a way to map molecules within cells and tissues. Using a single tissue section from a mouse model of Alzheimer’s as well as one from a normal mouse, they achieved unprecedented clarity, according to the paper.
In both mouse types, the research team assessed changes in metabolism and energy across distinct brain regions. Notably, in the Alzheimer’s model, they found signs of metabolic defects.
In addition, the researchers showed that metabolic demands vary from brain region to brain region, a concept that could amplify understanding of brain function and neurological disorders, they reported.
“Alzheimer’s doesn’t affect the brain evenly — different regions show different types of changes,” Sun said. “To effectively treat the disease, we need to identify and target the specific areas most affected based on a patient’s symptoms, rather than applying the same treatment across the whole brain.”
This study offers a roadmap for future research aiming to simultaneously analyze brain metabolism, fats and complex carbohydrates, providing a framework for investigations into both healthy and diseased brain tissue — one that could be adapted to study other tissues and diseases.
In addition, Sun said, this method has the potential to transform how metabolism is studied across scientific disciplines.