Physical activity delays onset of motor symptoms in the R61 mouse 体力活动延迟在R61鼠标运动症状发作

Physical activity delays onset of motor symptoms in the R61 mouse 体力活动延迟在R61鼠标运动症状发作 Physical activity delays onset of motor symptoms in the R6/1 mouse model of HD A new study conducted by researchers from the University of Oxford and the Howard Florey Institute, University of Melbourne shows that introducing an exercise wheel to the cages of the R6/1 HD mice at an early age delays the onset and progression of a number of motor symptoms. The new study builds on earlier work done by lead researcher Dr. Anthony J. Hannan and his colleagues on the effects of environmental changes on the HD mice (2004). They have previously shown that environmental enrichment, introduced at four weeks of age, delays the onset and progression of motor deficits, and reverses the reduction of BDNF (brain derived neurotrophic factor) in the striatum and hippocampus at five months of age. To enrich the environment, an object such as a small cardboard box open at one end or a plastic cone was placed in the cage and exchanged for another every two days. In another previous study (2006), Dr. Hannan and colleagues found that enhanced opportunities for physical activity, in the form of an exercise wheel introduced at ten weeks of age, just prior to expected onset of motor symptoms, had a lesser effect compared to that of environmental enrichment. In the new study, the exercise wheels were introduced much earlier, when the mice were only four weeks old. This time the effect was much larger. The onset of a number of motor deficits was significantly delayed, although performance on the accelerating rotarod, a standard measure, was not improved with voluntary exercise as it is with environmental enrichment. The study is important because it provides insights into research showing the importance of environmental factors on the age of onset in people. “Although HD has previously been considered to be a disease that is the epitome of genetic determinism, it is increasingly recognized that environmental factors can modulate disease onset and progression,” the researchers wrote. We already know, based on extensive analysis of data collected from HD families in Venezuela (2004), that there are environment effects on the age of onset of the disease. The number of CAG repeats is associated with the age of onset at the aggregate level. In general, those with a higher number will become symptomatic sooner than those with a lower number. However, it is not possible to predict age of onset for individuals because the age of onset for two people with the same CAG count often varies considerably. Some of the variation is genetic; there is good evidence that there are modifying genes. Other evidence points to environmental factors as another major influence. The age of onset can vary even with identical twins. The work of Dr. Hannan and colleagues suggests that positive environmental factors may include enhanced cognitive and sensory stimulation along with exercise and physical activities. Healthy exercise for physical fitness and lifelong learning look like good proactive strategies for the HD community. ????The study was published in the open-access journal BMC Neuroscience. To read it, go to BioMed Central: ? References Anton van Dellen, Patricia M Cordery, Tara L Spires, Colin Blakemore and Anthony J Hannan, “Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease.” BMC Neuroscience 2008 April 1, 9:34. T.Y.C. Pang, N.C. Stam, J. Nithianantharajah, M.L. Howard, and A.J. Hannan, “Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in huntington’s disease transgenic mice.” Behavioral Neuroscience 2006; 141(2): 569-584 Tara L. Spires, Helen E. Grote, Neelash K. Varshney, Patricia M. Cordery, Anton van Dellen, Colin Blakemore, and Anthony J. Hannan, “Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism.” The Journal of Neuroscience, 2004 March 3; 24(9): 2270-2276. The U.S.-Venezuela Collaborative Research Project and Nancy S. Wexler, “Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.” Proc Natl Acad Sci U S A. 2004 March 9; 101(10): 34983503. - Marsha L. Miller, Ph.D., April 1, 2008