|Imaging Neural Progenitor Cells in the Living
For the first time, investigators have identified a way to detect
neural progenitor cells (NPCs), which can develop into neurons
and other nervous system cells, in the living human brain using
a type of imaging called magnetic resonance spectroscopy (MRS).
The finding, supported by the National Institutes of Health (NIH),
may lead to improved diagnosis and treatment for depression, Parkinson's
disease, brain tumors, and a host of other disorders.
Research has shown that, in select brain regions, NPCs persist
into adulthood and may give rise to new neurons. Studies have suggested
that the development of new neurons from NPCs, called neurogenesis,
is disrupted in disorders ranging from depression and schizophrenia
to Parkinson's disease, epilepsy, and cancer. Until now, however,
there has been no way to monitor neurogenesis in the living human
"The recent finding that neural progenitor cells exist in
adult human brain has opened a whole new field in neuroscience.
The ability to track these cells in living people would be a major
breakthrough in understanding brain development in children and
continued maturation of the adult brain. It could also be a very
useful tool for research aimed at influencing NPCs to restore or
maintain brain health," says Walter J. Koroshetz, M.D., deputy
director of the NIH's National Institute of Neurological Disorders
and Stroke (NINDS), which helped fund the work. The study was also
funded by the NIH's National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK).
"This is the first noninvasive approach to identify neural
progenitor cells in the human brain," says Grigori Enikolopov,
Ph.D., of Cold Spring Harbor Laboratory in New York, a corresponding
author of the study. The work was conducted by co-corresponding
author Mirjana Maletic-Savatic, M.D.,Ph.D., of the State University
of New York, Stony Brook, Dr. Enikolopov, and colleagues at SUNY
Stony Brook and Brookhaven National Laboratory. MRS is an imaging
technique that can be used to detect proteins and other compounds
normally present in body fluids or tissues. The study results are
published in the November 9, 2007, issue of Science.
Previously developed techniques using positron emission tomography
and other types of brain imaging allow investigators to identify
NPCs in animals. However, those techniques require pre-labeling
the cells with radioactive agents or magnetic nanoparticles – strategies
that are not practical in people. In the new study, the researchers
identified an innate property of NPCs that can be detected by MRS.
This enables them to image NPCs without introducing drugs or other
The researchers used a technique related to MRS to compare the
signals of NPCs from embryonic mice to those of neurons, astrocytes,
and oligodendrocytes. Astrocytes and oligodendrocytes are non-neuronal
cells that are very common in the brain. The investigators found
that NPCs showed a specific signal, or marker, that was not as
common in other cell types.
Next, the researchers studied NPCs at various points as they differentiated
into other cell types in the laboratory. The level of the NPC signal
decreased over time, while the levels of other markers common in
neurons and astrocytes rose. The newly identified marker was more
common in brain cells from embryonic mice than in those from adult
mice. It also was more common in cells from the mouse hippocampus,
a region where neurogenesis occurs constantly, than in cells from
the brain's cortex, where new neurons are not normally formed.
Dr. Maletic-Savatic, Dr. Enikolopov and their colleagues then
gave adult mice a form of electrical stimulation that increases
the amount of neurogenesis in the brain. They found that the marker
they had identified increased significantly after the stimulation.
Additional results indicated that the marker is probably a mixture
of lipids (fatty acids), although the exact identity of the lipids,
and how they function in NPCs, is still undetermined.
The researchers then developed a signal processing method that
allowed them to separate the marker from other signals in the living
brain. They transplanted NPCs into the cortex of the adult rat
brain and found that they could clearly detect the marker in the
area where the NPCs were injected. They also found that it increased
Finally, the investigators tested their MRS imaging technique
in healthy people. They found major differences in the concentration
of the marker between the hippocampus and the cortex. They also
imaged the brains of pre-adolescents, adolescents, and adults and
found that the marker decreased with age.
The findings suggest that the marker identified in these experiments
can be used to detect NPCs and neurogenesis in the live human brain
using MRS. They also show that NPCs decrease during brain development.
Previous research had shown that neurogenesis decreases with age
in animals, but this is the first study to demonstrate that it
also decreases in the living human brain.
"This study identifies a novel biomarker and shows that we
can use it to see progenitor cells in the live brain," Dr.
Enikolopov says. "This protocol can now be used to study
a variety of problems." For example, researchers might study
people with depression to see if neurogenesis correlates with alterations
in depression or schizophrenia. The technique might also be used
to study changes that occur in neurological diseases such as traumatic
brain injury, stroke, epilepsy, and Parkinson's disease. It might
even be useful for detecting cancer, because researchers believe
some brain tumors are associated with aberrant proliferation of
NPCs, Dr. Enikolopov adds.
The researchers are now planning studies that will test the usefulness
of the new imaging technique in people with disease. They also
hope to improve their understanding of how the lipids they detected
function in NPCs and to refine the sensitivity of their technique.
Reporters: for more information, call 301-496-5924 or
go to www.ninds.nih.gov/PressRequest/.
The NINDS is the nation's primary funder of research on the brain
and nervous system. More information about pain and other neurological
disorders can be found on the NINDS web site, www.ninds.nih.gov/.
The NIDDK conducts and supports research in diabetes and other
endocrine and metabolic diseases; digestive diseases, nutrition,
and obesity; and kidney, urologic and hematologic diseases. For
more information about NIDDK and its programs, see www.niddk.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
 Manganas LN, Zhang X, Li Y,
Hazel RD, Smith SD, Wagshul ME, Henn F, Benveniste H, Djuric PM,
Enikolopov G, Maletic-Savatic M. "Magnetic Resonance Spectroscopy
Identifies Neural Progenitor Cells in the Live Human Brain." Science,
November 9, 2007, Vol. 318, No. 5852, p. 980.