Sci. Aging Knowl. Environ., 28 July 2004
Vol. 2004, Issue 30, p. nf70
[DOI: 10.1126/sageke.2004.30.nf70]


High Anxiety

Youthful stress impairs adult brain's ability to mint new cells

Mitch Leslie

Childhood hardship forges wiser, tougher adults--or so parents tell their whining children. But in rats, early stress can cause lasting harm to the brain. A new study shows that separating rat pups from their mothers slashes the adult rodents' production of new cells in a brain region crucial for memory and response to stress.

Setbacks early in life can undermine later health. For example, the offspring of rats stressed during pregnancy are prone to diabetes (see "From Womb the Bell Tolls"). And isolating young rats from their mothers for a few hours each day upsets regulation of stress hormones such as corticosterone. As adults, the rats produce longer-than-normal bursts of these molecules when under duress. The rodents also perform worse on learning tests. Researchers want to know how stress incites these effects. Previous work has shown that putting adult rats under pressure temporarily slows cell division in the hippocampus, an area that helps make memories and control anxiety. Neuroscientist Elizabeth Gould of Princeton University in New Jersey and colleagues tested whether early life adversity exerts prolonged effects on production of cells in that part of the brain.

The researchers put newborn rats through one of three regimes. Youngsters in one group were separated from their mothers for 3 hours every day. A second group went without maternal care for 15 minutes daily, and controls had unlimited access to mother love. When the rats reached adulthood, the researchers injected them with a chemical that tags newly formed cells. At different times after the injection, they killed some animals and scrutinized brain cells. Two hours or 1 week after the shot, the 3-hour group of maternally deprived rodents carried fewer labeled cells in the hippocampus, indicating that they hadn't created as many neurons as did the 15-minute lot or the controls. After 3 weeks, the numbers had evened out across groups, which hints that some fresh cells had died in the second two bunches.

Previous studies implied that stress hormones quell neuron production, so the researchers wondered whether lethargic cell division resulted from excessive quantities of these molecules. But the 3-hour group boasted normal amounts of blood corticosterone. To further probe corticosterone's impact on cell division, the researchers removed the rats' adrenal glands, which make the molecule. The team then adjusted the amounts of the hormone in the animals' blood by adding it to their drinking water. Reducing blood corticosterone below normal didn't boost cell output in the control or 15-minute group, but it did in the 3-hour group. The results suggest that instead of hiking stress hormones, separation from the mother makes the brain hypersensitive to them, says Gould.

The work shows that "early experience clearly affects the brain's ability to form new neurons," says neuroscientist Seymour Levine of the University of California, Davis. Now, researchers need to figure out the molecular mechanism, he adds. Gould's group is studying whether rearing rats in cages with many toys can counteract the impact of stress. Such work will show whether it's possible to prevent bad experiences from leaving a permanent scar.

July 28, 2004
  1. C. Mirescu, J. D. Peters, E. Gould, Early life experience alters response of adult neurogenesis to stress. Nat. Neurosci., 25 July 2004 [e-pub ahead of print]. [Abstract/Full Text]
Citation: M. Leslie, High Anxiety. Sci. Aging Knowl. Environ. 2004 (30), nf70 (2004).

Science of Aging Knowledge Environment. ISSN 1539-6150