Sci. Aging Knowl. Environ., 8 December 2004
Young at Brain
Long-lived mice pump out extra neurons
Miniature mice that survive 50% longer than normal boast another advantage over their full-sized counterparts. The puny mice's brains manufacture more new cells, according to new research. This cerebral fecundity might explain why the little rodents retain their memories unusually well.
Ames dwarf mice carry a mutation that stunts the pituitary gland. As a result, they produce scant growth hormone and insulin-like growth factor 1 (IGF-1), a molecule that helps regulate longevity in many organisms (see Bartke Viewpoint). A team led by endocrinologist Andrzej Bartke of the Southern Illinois University School of Medicine in Springfield showed that as the wee rodents got older, they outperformed normal mice on tests that measure how well an animal recalls a previous electric shock. Their memory prowess is mysterious because IGF-1 stimulates brain cell formation, or neurogenesis. Although the physiological importance of neurogenesis remains controversial, several studies have implied that boosting cell division sharpens recall in rodents. Results from Bartke's group suggested part of the solution--old Ames mice produce extra IGF-1 in the brain, even though little of the hormone circulates in their bodies. The researchers wanted to find out whether young Ames mice did the same and to determine whether the animals made extra neurons.
The researchers injected young adult rodents with a chemical that tags DNA of dividing cells. After a week of this treatment, the team sliced up the animals' brains and tallied the number of new cells in the hippocampus, a region that helps etch memories. The Ames mice had churned out about twice as many cells as had full-sized rodents. Many of the newborn cells sported a molecule found on mature neurons, suggesting that they were on their way to becoming functional. Like elderly Ames mice, the young animals carried above-normal quantities of IGF-1 in their brains, but the organ made paltry amounts of growth hormone. Profuse cell division might slow cognitive decline as the diminutive creatures age, the researchers conclude. Combined with previous findings, the work might also resolve the apparent paradox of how the mice retain their memories despite a general IGF-1 scarcity . "In the hippocampus, where leaning and memory 'happen,' it appears that there is never a deficiency of IGF-1," says Bartke. How the brain can fashion plenty of IGF-1 remains unknown.
"It's a big step toward understanding the preservation of cognitive function," says endocrinologist Holly Brown-Borg of the University of North Dakota in Grand Forks. The study also clarifies the connection between growth hormone and IGF-1, suggesting that growth hormone doesn't control IGF-1 in the brain, as it does in the rest of the body, she says. "It's an interesting result," says neuroscientist Mark Mattson of the National Institute on Aging branch in Baltimore, Maryland. However, he cautions, most fresh brain cells die quickly. We need further research to show that newborn cells integrate into brain circuits, Mattson says. He also wants to see additional evidence that IGF-1 drives the increase in cell division because many triggers, including exercise and other brain chemicals, can spur neurogenesis. That work might clarify why these little mice have such big memories.
December 8, 2004
Suggested by Christina Craig-Veit and James M. Harper.
Science of Aging Knowledge Environment. ISSN 1539-6150