It was long believed that once the brain stopped developing, so did its ability to produce new neurons. But scientists began debating the matter in the early 1960s when claims of fresh neurons in an adult brain surfaced. Since then, evidence for so-called neurogenesis has snowballed, culminating in the 1998 discovery that cells were replicating in the horseshoe-shaped hippocampus region of the cerebrum of five cancer patients.
Scientists had found new neurons, or nerve cells, in the olfactory bulbs (structures located on either side of the forebrain involved in processing odors) of other mammals, leading them to suspect that humans might have them there, too. Researchers, however, could not locate the pathway, found in the other animals, between the cerebrum in the center of the human brain (where neural stem cells are created) and the forebrain, where they morph into neurons.
This week, scientists from New Zealand and Sweden report they not only located this elusive passageway—called the rostral migratory stream (or RMS)—in the human brain, but also found cells in the process of differentiating into neurons along this structure.
"We suspect [the cells] may be following this tube because the tube is filled with liquid that contains some kind of growth factor or some type of attractant," says Peter Eriksson, a neuroscientist at Sahlgrenska Academy at G¿teborg University in Sweden and co-author of the study appearing in this week's issue of Science. "From animal studies, it's very obvious that if you have an insult [to] the brain, there are a number of molecular signals that tells the stem cells to start dividing and to start migrating and perhaps also to start repopulating areas of injury."
The researchers began their search for the rostral migratory system by dissecting 30 postmortem brains—from people ranging in age from 20 to 80—and aiming high-powered microscopes at roughly the same area where they had located the RMS in rat brains. The RMS links the olfactory bulbs to the lateral walls of the brain's ventricles (at the base of the brain where it connects to the spinal cord), which produce the cerebrospinal fluid that cushions the two nervous system constituents. To their surprise, they found pathways of proliferating cells, and then confirmed the location of the streams (one on the side of each olfactory bulb) using magnetic resonance imaging (MRI) in six living patients.
Eriksson says the RMS canals travel "down and back" from the ventricles, "and then take a sharp turn into the olfactory track and bulbs." The 17-millimeter (around two thirds of an inch) route from the subventricular zone to the olfactory tract is different than its rodent counterpart, he adds, likely because of the larger size of the human forebrain. Researchers found an average of about 110,000 cells at different stages of development along the route. By the time the cells arrived at the olfactory bulbs, they were well on their way to becoming neurons.
"There was some controversy about adult human neurogenesis in the olfactory bulb," says Fred Gage, a biologist at the Salk Institute for Biological Studies in La Jolla, Calf., and former collaborator with Eriksson on the 1998 paper on neurogenesis in cancer patients. "But, this recent manuscript is very persuasive." Pasko Rakic, a neurobiologist at the Yale University School of Medicine, says these findings "basically confirm several previous studies" that there is a small, but existing RMS. "This doesn't come as a surprise to me," he adds, "because we have seen a present, but very small one, compared to rodents, in nonhuman primates."
The bottom line: "My paper establishes the existence of the RMS in the human brain," Eriksson says, noting that it also confirms a 2004 paper in the journal Developmental Brain Research showing neurogenesis in the olfactory bulb.
Now that the team has located the RMS trail, Eriksson says researchers can begin to assess whether the quantity of new neurons in the olfactory bulb has any effect in neurodegenerative disease. In the Science paper, the authors note that a reduction in the number of new neurons created in the olfactory bulbs cause rodents to have difficulty discriminating odors, a symptom in humans that may be a harbinger of Parkinson's disease. (Eriksson hypothesizes that new brain cells take up residence in the olfactory bulbs, because continuous renewal of cells may be needed to process the myriad scent molecules encountered during life. Neurons stored here could conceivably be recruited to injury sites if the brain suffers damage.)
"The first question," Eriksson says, "would be to see if there are differences between normal, healthy subjects and subjects [who] have had a stroke or some kind of insult [to] the brain to figure out whether we actually do get activation of stem cells also in the human brain."