ADVANCES ON HOW NEURONS ARE BORN IN THE BRAIN YIELD HOPE FOR TREATING BRAIN DISEASES AND ENHANCING THINKING ABILITY
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ADVANCES ON HOW NEURONS ARE BORN IN THE BRAIN YIELD HOPE FOR TREATING BRAIN DISEASES AND ENHANCING THINKING ABILITY
WASHINGTON, DC, November 15, 2005 — New studies about how neurons are born and mature in the adult brain yield hope for treating neurodegenerative diseases and for enhancing cognitive function. The findings could pave the way for better cell replacement therapies—including those using stem cells—for injured or lost neurons.
Most neurons in the adult are born and develop in the embryo or soon after birth. We are unable to regenerate and replace many of these cells as adults. However, neurons in some areas of the brain—including those involved in learning and memory—continue to be born well after birth, sometimes right up into our 70s, if the right environmental conditions are present.
“The human brain is quite plastic—or capable of adjusting to its environment,” says Ira B. Black, MD, of the University of Medicine and Dentistry of New Jersey in Piscataway, NJ. “This capability for developing new neurons reminds us of the importance of tending to brain health through activities such as exercise and learning and memory tasks.” A mini-symposium on “New Neurons in the Adult Mammalian Brain: Synaptogenesis and Functional Integration” will be held at Neuroscience 2005.
Although it has been clear for some time that the brains of humans and other mammals can produce new neurons, the function of these neurons has not been clear.
Previous studies showed that new neurons are more excitable than their “old” neighboring cells, and that they can easily form new synapses, the critical junctures where information can transfer from one neuron to another.
New neurons are also better able to fine tune their processing of information, which may help in the learning of new memories, according to Josef Bischofberger, PhD, of the University of Freiburg in Germany and his colleagues.
Bischofberger and his colleagues tagged with a fluorescent protein young neurons in the hippocampus of mice. The hippocampus is a brain area involved in learning and memory. They found that young neurons were better able to strengthen their synaptic connections with other neurons when necessary to form a lasting connection, a capability important for the formation of new memories.
New neurons were also better able than mature neurons to reduce the strength of their synaptic connections when they received impulses just below the threshold needed for a nerve impulse to fire. Mature neurons did not adjust their synaptic strength when treated in the same manner.
“These new neurons can form highly flexible synaptic contacts with other neurons in the nervous system,” Bischofberger says. “This might be especially important for the rapid formation of new memories.”
In other work, scientists are shedding light on how newborn neurons can be successfully integrated into the adult brain, not a trivial feat given the already well-established network of neural connections.
Newly generated neurons follow a fixed pattern of integration into the existing brain circuitry, according to Hongjun Song, PhD, and Guo-li Ming, PhD, of the Institute for Cell Engineering at Johns Hopkins University in Baltimore, MD. Knowing this pattern could help in cell replacement therapies that use neurons derived from both embryonic and adult stem cells, Song says. Stem cells are the basic building blocks of the body from which all other cells are formed, including those for organs, blood, and nerves.
Song, Ming, and their associates genetically marked newborn neurons called granule cells in the dentate gyrus of adult mice. This brain region is involved in learning and memory. They found that as the newborn neurons integrated into the brain, they received a sequence of inputs that helped regulate their firing.
“For new neurons generated from stem cells to successfully integrate into the brain, they may need to follow such a pattern as well,” Song says.
Understanding the sequence of events that occur as adult brain stem cells develop into new neurons could help in gauging how activities such as new learning and exercise affect the brain, says Gerd Kempermann, MD, of the Max Delbrück Center for Molecular Medicine in Berlin, Germany.
Kempermann has identified several stages adult stem cells in the hippocampus must go through before they become neurons. A stem cell itself rarely divides, but its daughter cell, the so-called progenitor cell, divides frequently and vastly expands the pool of proliferating precursor cells that may become neurons. These cells begin to show the first signs of maturing into neurons. When they stop dividing, some begin to make functioning connections with other neurons; the others are eliminated.
“Both these stages of new neuron development—the expansion of precursor cells and the recruitment of new neurons—can be affected by activities such as exercise and learning tasks,” Kempermann says. “Physical exercise, for example, can increase precursor cell proliferation, while learning may affect the survival of new neurons.”
In other work showing that environmental conditions affect development of new neurons, Linda Overstreet Wadiche, PhD, and her colleagues of the Vollum Institute at Oregon Health and Science University in Portland, OR, found that aging and seizures can affect the rate at which new neurons integrate into the brain.
The investigators labeled with a temporary fluorescent tag newborn neurons in the hippocampus of mice of different ages. The neurons lose the label as they get older, allowing the investigators to distinguish new neurons from more mature neurons. They found that newborn neurons in adult and neonatal mice had the same functions, but that they developed more slowly in adults. The neonatal mice had a pattern of brain activity that was not present in adult mice.
Wadiche and her colleagues then set out to determine whether newborn neurons mature faster in neonatal mice as a result of their pattern of brain network activity. In one experiment, they reduced the neonatal pattern of network activity. In a second experiment, they induced seizures in mice using a method that models human temporal lobe epilepsy. Both manipulations changed how newborn neurons matured. Reduced network activity in neonates slowed down neuronal maturation. Conversely, seizures in adults caused new neurons to mature quickly and to rapidly form synapses, sometimes with inappropriate neuron partners.
“These results could provide insights into ways that neural stem cells can be encouraged to correctly wire into diseased brain networks,” Wadiche says. “And, given the mounting evidence that newborn neurons in adults are important for cognitive functions, finding ways to help newborn neurons integrate into existing brain circuits might help enhance cognitive abilities as well.”
