Can the brain be protected through exercise? Lessons from an animal model of parkinsonism.
Evidence suggests that following injury the brain has the capacity for self-repair and that this can be promoted through a variety of experiences including motor activity. In their article, Döbrössy and Dunnett have provided further evidence that this is the case in an animal model in which an excitotoxin is applied to the neostriatum. Under standard conditions, such a toxin would cause considerable damage to the GABAergic cells of this region and produce behavioral deficits. This model has been used to explore certain aspects of Huntington's disease, which also involves the loss of these neurons. However, Döbrössy and Dunnett show that the damage can be reduced by prior motor training. We have been exploring the neuroprotective effects of motor exercise in a different model, one involving 6-hydroxydopamine, which normally destroys dopamine neurons. Our results indicate that forced exercise can reduce the vulnerability of dopamine neurons to 6-hydroxydopamine. The results further suggest that this protection is due in part to an increase in the availability of the trophic factor GDNF, which can in turn stimulate certain signaling cascades, including one that activates ERK. Our results, together with those of Döbrössy and Dunnett and others, raise the possibility that exercise will protect against a variety of neurodegenerative conditions.
Smith
Amanda D
AD
Department of Neurology, Pittsburgh Institute for Neurodegenerative Disease, University of Pittsburgh School of Medicine, Pittsburgh, PA 15217, USA.
Zigmond
Michael J
MJ
D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000517:prevention & control*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology; D013565:Sympatholytics / Q000633:toxicity; D009435:Synaptic Transmission / Q000187:drug effects
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D013565:Sympatholytics; D016627:Oxidopamine