In today's online edition of Annals of Neurology, researchers report that a form of neuroplasticity-namely the birth of new neurons in the brain's hippocampus-can be continuously stimulated by an active, challenging lifestyle throughout the second half of life, at least in mice. The study, by Gerd Kempermann and Daniela Gast of the Max-Delbrueck Center for Molecular Medicine in Berlin, with Fred Gage of the Salk Institute in La Jolla, California, follows earlier work by these investigators that had shown a spike in hippocampal neurogenesis and concomitant improvements in learning after short-term stimuli, such as three weeks of voluntary wheel running (van Praag et al., 1999a; van Praag et al., 1999b.)

This research area attempts to find a cellular explanation for human epidemiologic data showing that people who lead an active lifestyle, both physically and mentally, reduce their risk of developing dementia (Berkman et al.1993; Laurin et al., 2001, see related news item). The hypothesis holds that a high level of activity somehow increases an existing baseline level of neurogenesis in the dentate gyrus of the adult hippocampus, a brain region key to learning and memory. This study was important because prior work had left unclear the question whether neurogenesis increases only temporarily in response to acute changes in the environment, or whether sustained, long-term increases are possible.

Kempermann et al. housed 10-month-old, or middle-aged, mice either in standard, bare cages, or in larger cages with a running wheel, tunnels, and other play objects that were changed periodically. To create a difference in social interactions, as well, control mice lived with few cage-mates, "enriched" mice with many. Ten months later, the authors found that the "enriched", and now elderly, mice had five times the net neurogenesis of the control mice. This increase was partly due to improved survival of the newly born neurons (see also today's story above) and came at the expense of newly generated astrocytes, of which there were fewer in the enriched mice. Moreover, the enriched group had 50 percent less lipofuscin pigment deposits in their hippocampal granule neurons. (Thought to be an indicator of chronic oxidative stress, lipofuscin is used as a general marker of brain aging.) Finally, the enriched mice were a little lighter, more exploratory, and appeared to have stronger locomotor skills and endurance.

These data mean that although hippocampal neurogenesis normally declines with age, the aging brain retains the plastic potential to respond to activity, and do so continuously, the authors write. This applies even if intense activity and exercise begins only in middle age, The study also appears to support the controversial view that adult neurogenesis in the hippocampus is more than a functionally insignificant small trickle, but indeed is one of the factors that determine the health of the aging brain. However, Kempermann notes that to the extent these animal data have meaning for humans, they suggest preventive activity and exercise, as it remains unclear whether neurogenesis could ever bring back cognitive function that was lost once scores of neurons have died.—Gabrielle Strobel

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References

External Citations

  1. van Praag et al., 1999a
  2. van Praag et al., 1999b
  3. Berkman et al.1993
  4. Laurin et al., 2001

Further Reading

Primary Papers

  1. . Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol. 2002 Aug;52(2):135-43. PubMed.