This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Alzheimer's disease is best known for its effects on memory and cognition, but the disease also involves changes in how brain cells produce and use energy. Mitochondria, the structures that supply much of a cell's energy, can become dysfunctional in Alzheimer's disease.
At the same time, changes in blood flow and oxygen availability may place additional demands on brain tissue. Understanding how these processes interact could help researchers characterize metabolic changes that accompany the disease. A recent study published in Neurophotonics examines these processes together in the living brain.
Researchers in Ammasi Periasamy's group at the University of Virginia (UVA) combined two forms of two-photon lifetime microscopy to measure cellular metabolism and oxygen levels in the cerebral cortex of mice. They compared Alzheimer's disease model mice with healthy, wild-type mice. The approach addresses an important difficulty in studying brain metabolism.
Oxygen supply and cellular energy production are closely related, but measurements of one do not necessarily reveal what is happening to the other. By collecting both types of information at the same time, the researchers could examine how metabolic activity relates to oxygen availability within the same living tissue. To track cellular metabolism, the team used two-photon fluorescence lifetime imaging microscopy, or FLIM.
Rather than simply measuring the brightness of fluorescence, FLIM measures how long fluorescent molecules remain in an excited state before releasing light. The researchers focused on NAD(P)H, a naturally occurring molecule involved in cellular energy production. NAD(P)H can exist either freely within cells or bound to proteins, and these states have different fluorescence lifetimes.
The study used the proportion of protein-bound NAD(P)H as an indicator of mitochondrial metabolic activity. Because NAD(P)H occurs naturally in cells, its fluorescence provides a way to examine metabolism without introducing a fluorescent label specifically for that measurement. The second technique, phosphorescence lifetime imaging microscopy, or PLIM, provided information about oxygen.
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