Fifteen years ago, researchers thought there was no such thing as adult neural stem cells. The adult brain, so the theory went, had no way of replacing neurons lost to the ravages of time, injury or controlled substances.
These days, researchers have done a 180 degree turnaround on that idea. Not only are neural progenitor cells - which are not strictly speaking stem cells, but can differentiate into several different cell types - an accepted part of scientific wisdom, they are thought to be important in diseases ranging from depression and schizophrenia to Parkinson's disease, epilepsy and cancer.
And in the Nov 9, 2007, issue of Science, researchers from SUNY Stony Brook, Brookhaven National Laboratory, and Cold Spring Harbor Laboratory reported on a new method to see those neural progenitor cells that opens up the possibility of studying them in a much broader variety of contexts than before.
The researchers used a variant of magnetic resonance imaging, but co-author Grigori Enikolopov told BioWorld Today that the technique is "not strictly speaking imaging." Instead he and his colleagues, including senior author Mirjena Maletic-Savatic, use magnetic resonance spectroscopy, which analyzes the magnetic properties of nuclei, to see a unique signal that is generated by neural progenitor cells, along with an analysis algorithm that is able to see a "very, very weak signal among a lot of noise," Enikolopov explained.
Maletic-Savatic and her colleagues first identified that signal by studying neural progenitor cells in culture, searching for "any metabolite that would allow us to recognize neural stem cells," Enikolopov explained.
Once the team had identified a marker - which appears to be a mix of fatty acids, though its exact role in neural progenitor cells remains unclear for now - the researchers conducted "a series of experiments trying to show that what we see correlates with the presence of progenitor cells," Enikolopov said.
They first studied neural progenitor cells at various points as they differentiated. The level of the progenitor marker decreased over time, while the levels of other markers that identify different types of differentiated cells increased.
The marker is more common in brain cells from embryonic mice than in those from adult mice. It also is more common in cells from the hippocampus, a region where neurogenesis occurs in adults, than in cells from the brain's cortex, where new neurons are not normally formed in adults.
Maletic-Savatic, Enikolopov and their colleagues next treated mice with electroconvulsive stimulation, a form of electrical treatment that sometimes is used to treat severe depression and leads to the formation of new neurons. They found that the marker they had identified increased significantly after the stimulation.
When the scientists transplanted neural progenitor cells into the cortex of the adult rat brain, where neurons are not usually formed, they found that they clearly could detect the marker in the area where the progenitor cells were injected.
As a final critical test, the researchers took their technique into humans. As in the animal studies, and in agreement with what is known about neurogenesis in the adult brain, the hippocampus contained higher levels of marker than the cortex. When the scientists compared adolescents to adults, they found "a dramatic decrease" in the level of the marker with the age of the subject. In people whose routine as not changing, the concentration of the marker remained stable over a period of months, showing that the technique is sensitive enough to be used in longitudinal studies.
Enikolopov said that the researchers are looking for spectroscopic signals that could identify other cells types as well, and are particularly interested in a way to identify microglia.