Of All the Nerve: Old brains grow new working cells (Neurobiology)
Authors: Beckman Mary 
Published: August 2003

Several years ago, scientists realized that new neurons can grow in the brains of mice, but they were unable to show that the newborn cells worked. Now, scientists have found that these rookies mature, connect with other neurons, and even fire like they are in their prime. The work shows that fresh brain cells are more than just for show.

To gather evidence that the brain can pump out virgin cells, scientists typically inject animals with a compound that is taken up only by cells that are dividing. After the animals die, the researchers slice up the brain and look for cells that contain the compound and bear molecular characteristics of neurons. This technique has pinpointed cells arising in the hippocampus--where memories are acquired--of mice, rats, monkeys, and humans. But these snapshots of new growth didn't reveal whether the cells behaved properly.

To identify and test new cells in action, van Praag and colleagues engineered a retrovirus to produce green fluorescent protein (GFP). The retrovirus infects only dividing cells and allows GFP to be produced as long as the cell is alive. The team anticipated that the iridescent protein would reveal not only the cell body but also its sinuous extensions that communicate with other neurons. GFP's glow would thus show where the cell lies in the brain and whether it contacts other nerve cells. Previous studies had established that exercise could spur the birth of new brain cells, so the researchers injected the engineered retrovirus into the hippocampus of adult mice that ran on an exercise wheel; a second group of mice with no running wheel served as controls.

At varying times after injection, the researchers dissected the brains of both the active and sedentary mice and looked for luminous cells. They identified nerve cells by testing for diagnostic marker proteins. Although new, GFP-loaded cells arose within 48 hours in both groups of mice, the busy mice sported more types of neurons than did the idle animals. All of the 48-hour-old cells were immature--but animals that were allowed to grow for 4 weeks after injection boasted green glowing cells that carried molecular markers indicating that the youngsters had grown up. High-resolution microscopy showed that the new cells had made connections with other neurons, and electrophysiological tests established that they fired spontaneously--and as often as normal cells do. The 4-week-old nerve cells took up only 60% of the space of normal neurons, however, suggesting that the newcomers hadn't matured. Four months after injection, GFP-brimming neurons in a third group of animals had made up the size difference.

No one has performed similar tests in humans, but previous work by a team from the same laboratory took advantage of patients up to 70 years old who had been injected with a compound to follow their brain tumor growth. By detecting the compound after death, the neuroscientists identified new neurons in the hippocampus. Together with the new findings, these results hint that people can grow active neurons throughout their lives.

Developmental neurobiologist Pasko Rakic of Yale University says the researchers provide "pretty strong evidence" for new working neurons. "[The work] is beautifully illustrated, convincingly documented," he says. The researchers "show very clearly the functional incorporation of these cells."

--Mary Beckman

H. van Praag, A. F. Schinder, B. R. Christie, N. Toni, T. D. Palmer, F. H. Gage, Functional neurogenesis in the adult hippocampus.
Nature
415
, 1030-1034 (2002).
[Abstract]
[Full Text]

Further Reading

• M. Barinaga, Neurons arise in adult brains.
Science
NOW, 29 October 1998.
http://sciencenow.sciencemag.org/cgi/content/full/1998/1029/1

• Fred Gage's Web page
http://www.salk.edu/faculty/gage.html

• The Whole Brain Atlas
http://www.med.harvard.edu/AANLIB/home.html