For years the dogma stood that the brain consisted of all its neurons from birth and received no subsequent production of new neurons (neurogenesis) in adult life. What started with the discovery of neurogenesis in songbirds 20 years ago, which allowed the birds to form memories for new songs (Marler 1998) has now led to discovery of neurogenesis in mice, rabbits, monkeys and humans (). This new neuronal birth is limited to the 2 regions of the brain being the hippocampus and the subventricular zone. Interestingly both these areas have been shown to possess stem cells (Conover et al 2003) which underpins the mechanism allowing new neuronal production. It has also been shown that diseases such as dementia display widespread cell atrophy and that environmental enrichment and exercise can manipulate neurogenesis and cell death pathways to help delay disease progression (Hannan et al 2008). It has also been recently shown that exercise can help fight dementia in the human population delaying cognitive decline(Nicola et al 2008). These results are extremely encouraging and potentially could allow therapies for sufferers through specific exercise and or environmental enrichment programs.
The flow of papers now coming through outlining the beneficial effects of exercise in delaying dementia is extremely encouraging, but it is still unclear the exact mechanism by which it does this. It is possible exercise exerts its effects through increased blood flow to the brain (Phelp et al 2001), preventing strokes which subsequently stops progression into dementia, the up regulation of neurogenesis (Hannan et al 2003) or a combination of all these factors. What also is unclear, which will unfold over the next few years, is what the best exercises are to maximize the positive benefits. But for now we are seeing that 15 minutes of exercise whether walking, calisthenics or swimming 3 times a week gives a 38% less likely chance of developing dementia (Gaia Vince 2006), which is very encouraging.
Dementia is characterized by severe cell atrophy in the brain and cognitive decline (Kuhn et al 2007) with Parkinson’s, Alzheimer’s and Huntington’s disease all falling under this dementia banner. In relation to treatment through exercise it has been shown that environmental enrichment (EE) which includes exercise can delay onset and progression of Huntington’s disease (HD) in a mouse model (Hannan 2004). At a cellular level it has been shown to up regulate critical neurotrophic factors such as BDNF which are molecules which modulate brain plasticity and health. This up regulation of BDNF to normal levels also corresponded with the return of low neurogenesis activity in the HD mice to normal levels. So it is possible that the dementia seen is caused by a failure of new neuron production and integration into the brain over time (demonstrated by lower neurogenesis rates), which can subsequently be rescued by environmental enrichment and exercise to help delay onset.
The big question is to what degree up regulation of neurogenesis in the hippocampus will combat dementia and can this effect be further manipulated by other treatments that utilize the same pathway, like antidepressants. Interestingly antidepressants have been shown to have the same mechanism to fight depression as exercise, up regulating BDNF levels and promoting neurogenesis in the hippocampus (Peng et al 2008). Or can sustained exercise over a lifetime be more beneficial to fight dementia?
What is known at present is that exercise and environmental enrichment have a positive effect in preventing Dementia. The exact mechanism it exerts this effect is not clearly understood, but with the systems being investigated eventually the underlying pathway will be found. Knowing these pathways will allow even better therapies to be implemented. On one hand you have dementia which is characteristically caused by neuronal failure and cell death and on the other hand you have tools to help fight the condition through manipulation and strengthening of the system. Right now it seems like exercise and healthy living are at the best tools on hand to fight the condition. And with time we will find out exactly how it achieves this.
Geoff Turnbull Neuroscientist
BSC: Maj Biomedical Sciences, Hons Anat, PHD Pending IN Neuroscience
Blakeslee, Sandra. “Decade of Discovery Yields a Shock About the Brain.” New York Times, January 4, 2000.
Eriksson, PS., et.al. “Neurogenesis in the adult human hippocampus.” Nat Med. Novemeber 4, 1998.
Gaia Vince Annals of Internal Medicine (vol 144, p 73)
Int J Geriatr Psychiatry. 2006 Oct;21(10):977-82 Demonstration of cognitive decline in Parkinson’s disease using the Cambridge Cognitive Assessment (Revised) (CAMCOG-R).
Gould, E., et.al. “Neurogenesis in the Neocortex of Adult Primates.” Science. October 15, 1999.
Gould, E., et. al. “Neurogenesis in the Dentate Gyrus of the Adult Tree Shrew Is Regulated by Psychosocial Stress and NMDA Receptor Activation.” The Journal of Neuroscience. April 1, 1997.
Gould, E., et. al. “Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress.” Proceedings of the National Academy of Sciences. March 17, 1998.
Hannan Tony. Society for Neuroscience (2004, March 10). Environmental Enrichment Lessens Protein Deficits In Mouse Model Of Huntington’s
Howard Florey Institute (2008, January 29). Mental And Physical Exercise Delays Dementia In Fatal Genetic Disease. ScienceDaily.
J Physiol Volume 533, Number 3, 849-859, June 15, 2001 Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine
Jessica B Lennington,1 Zhengang Yang,2 and Joanne C Conover 1Reprod Biol Endocrinol. 2003; 1: 99. Neural stem cells and the regulation of adult neurogenesis
Kornack, D. and P. Rakic. “Continuatoin of neurogenesis in the hippocampus of the adult macaque monkey.” Proceedings of the National Academy of Sciences, May 11, 1999.
Kuhn HG, Cooper-Kuhn CM, Boekhoorn K, Lucassen PJ. Eur Arch Psychiatry Clin Neurosci. 2007 Aug;257(5):281-9 Changes in neurogenesis in dementia and Alzheimer mouse models: are they functionally relevant?
Kuhn, Thomas. Philosopher of science.
Michael D. Delp, R. B. Armstrong, Donald A. Godfrey *, M. Harold Laughlin †, C. David Ross ‡ and M. Keith Wilkerson
Nicola T. Lautenschlager, MD; Kay L. Cox, PhD; Leon Flicker, MBBS, PhD; Jonathan K. Foster, DPhil; Frank M. van Bockxmeer, PhD; Jianguo Xiao, MD, PhD; Kathryn R. Greenop, PhD; Osvaldo P. Almeida, MD, PhD. JAMA. 2008;300(9):1027-1037. Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease
Peng Q, Masuda N, Jiang M, Li Q, Zhao M, Ross CA, Duan W. Exp Neurol. 2008 Mar;210(1):154-63. Epub 2007 Nov 9 The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington’s disease mouse model.
Peter Marler Nature 334, 106 – 107 (14 July 1988); doi:10.1038/334106a0 Birdsong and neurogenesis
Peter S. Eriksson1, 4, Ekaterina Perfilieva1, Thomas Björk-Eriksson2, Ann-Marie Alborn1, Claes Nordborg3, Daniel A. Peterson4 & Fred H. Gage4Nature Medicine 4, 1313 – 1317 (1998) Neurogenesis in the adult human hippocampus
Sci Am. 1989 Feb;260(2):74-9. From bird song to neurogenesis.
Wade, Nicholas. “Brain May Grow New Cells Daily” New York Times, October 15, 1999.