Exercise Increases Brain Growth Factor and Receptors, Prevents Stem Cell Drop in Middle Age

The American Physiological Society released the following announcement:

Exercise increases brain growth factor and receptors, prevents stem celldrop in middle age
BETHESDA, Md. (Nov. 18, 2008)

A new study confirms that exercise canreverse the age-related decline in the production of neural stem cellsin the hippocampus of the mouse brain, and suggests that this happensbecause exercise restores a brain chemical which promotes the productionand maturation of new stem cells.Neural stem cells and progenitor cells differentiate into a variety ofmature nerve cells which have different functions, a process calledneurogenesis. There is evidence that when fewer new stem or progenitorcells are produced in the hippocampus, it can result in impairment ofthe learning and memory functions. The hippocampus plays an importantrole in memory and learning.The study, "Exercise enhances the proliferation of neural stem cells andneurite growth and survival of neuronal progenitor cells in dentategyrus of middle-aged mice," was carried out by Chih-Wei Wu, Ya-TingChang, Lung Yu, Hsiun-ing Chen, Chauying J. Jen, Shih-Ying Wu, Chen-PengLo, Yu-Min Kuo, all of the National Cheng Kung University MedicalCollege in Taiwan. The study appears in the November issue of theJournal of Applied Physiology, published by The American PhysiologicalSociety.

Rise in corticosterone or fall in nerve growth factor?The researchers built on earlier studies that found that the productionof stem cells in the area of the hippocampus known as the dentate gyrusdrops off dramatically by the time mice are middle age and that exercisecan slow that trend. In the current study, the researchers wanted totrack these changes in mice over time, and find out why they happen.

One hypothesis the researchers investigated is that the age-relateddecline in neurogenesis is tied to a rise in corticosterone in middleage. Elevation of corticosterone has been associated with a drop in theproduction of new stem cells in the hippocampus.The second hypothesis is that nerve growth factors -- which encouragenew neural cell growth but which decrease with age -- account for thedrop in neurogenesis. Specifically, the study looked at whether adecrease in brain-derived neurotrophic growth factor leads to a declinein new neural stem cells.Variables studied.

The researchers trained young (3 months), adult (7 months), early middle-aged (9 months), middle-aged (13 months) and old (24 months) mice to runa treadmill for up to one hour a day.The study tracked neurogenesis, age, exercise, serum corticosteronelevels and brain-derived neurotrophic factor (BDNF) and its receptorTrkB levels in the hippocampus. The researchers focused on middle age asa critical stage for the decline of neurogenesis in the mice. As expected, the study found that neurogenesis drops off sharply inmiddle-aged mice. For example, the number of neural progenitor andmitotic (dividing) cells in the hippocampus of middle-aged mice was only5% of that observed in the young mice.The researchers also found that exercise significantly slows down the loss of new nerve cells in the middle-aged mice. They found thatproduction of neural stem cells improved by approximately 200% comparedto the middle-aged mice that did not exercise. In addition, the survivalof new nerve cells increased by 170% and growth by 190% compared to thesedentary middle-aged mice.

Exercise also significantly enhanced stemcell production and maturation in the young mice. In fact, exerciseproduced a stronger effect in younger mice compared to the older mice.How does this happen?Based on these results, it appears that nerve growth factor has more todo with these findings than the corticosterone:

* The middle-aged exercisers had more brain-derived neurotrophicfactor and its receptor, TrkB, compared to the middle-aged mice that didnot exercise. This suggests that exercise promotes the production ofbrain-derived neurotrophic factor which, in turn, promotesdifferentiation and survival of new brain cells in the hippocampus.

* Exercise did not change the basal level of serum corticosterone inmiddle-aged mice. This suggests that the reduction of neurogenesisduring aging is not due to the drop in corticosterone levels.