Limits...
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.

van Dellen A, Cordery PM, Spires TL, Blakemore C, Hannan AJ - BMC Neurosci (2008)

Bottom Line: We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age.These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment.However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK. anthony.hannan@florey.edu.au

ABSTRACT

Background: Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit.

Results: We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running.

Conclusion: These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.

Show MeSH

Related in: MedlinePlus

Wheel running does not delay the onset of a motor co-ordination deficit measured on the accelerating rotarod test. A) On the accelerating rotarod, neither the HD mutation nor wheel running (P = 0.68) had any affect on motor performance of HD mice at 3 months of age. B) The motor deficits which had developed in HD mice at 5 months of age were not affected by wheel running (P = 0.72). NE: non-enriched; RW: running wheel; WT: wild-type; HD: Huntington's disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2335112&req=5

Figure 2: Wheel running does not delay the onset of a motor co-ordination deficit measured on the accelerating rotarod test. A) On the accelerating rotarod, neither the HD mutation nor wheel running (P = 0.68) had any affect on motor performance of HD mice at 3 months of age. B) The motor deficits which had developed in HD mice at 5 months of age were not affected by wheel running (P = 0.72). NE: non-enriched; RW: running wheel; WT: wild-type; HD: Huntington's disease.

Mentions: At 3 months of age, neither the HD mutation nor wheel running had a significant effect on accelerating rotarod performance (Fig. 2A). Despite the fact that exercise on a running wheel is superficially similar to the testing paradigm of the accelerating rotarod, mice engaged in this form of exercise from a juvenile age did not improve performance on the rotarod in either wild-type or HD mice at 5 months of age (Fig. 2B; wheel running: F [1, 25] = 0.40, P = 0.72; 2-way ANOVA). At 5 months, an effect of the HD mutation on performance was observed (Fig. 2B; HD: F[1, 28] = 8.58, P < 0.01; 2-way ANOVA). These results are consistent with, and extend, the recent finding that wheel running starting at an adult age has no effect on progression of rotarod deficits measured from 15–20 weeks of age [14].


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.

van Dellen A, Cordery PM, Spires TL, Blakemore C, Hannan AJ - BMC Neurosci (2008)

Wheel running does not delay the onset of a motor co-ordination deficit measured on the accelerating rotarod test. A) On the accelerating rotarod, neither the HD mutation nor wheel running (P = 0.68) had any affect on motor performance of HD mice at 3 months of age. B) The motor deficits which had developed in HD mice at 5 months of age were not affected by wheel running (P = 0.72). NE: non-enriched; RW: running wheel; WT: wild-type; HD: Huntington's disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2335112&req=5

Figure 2: Wheel running does not delay the onset of a motor co-ordination deficit measured on the accelerating rotarod test. A) On the accelerating rotarod, neither the HD mutation nor wheel running (P = 0.68) had any affect on motor performance of HD mice at 3 months of age. B) The motor deficits which had developed in HD mice at 5 months of age were not affected by wheel running (P = 0.72). NE: non-enriched; RW: running wheel; WT: wild-type; HD: Huntington's disease.
Mentions: At 3 months of age, neither the HD mutation nor wheel running had a significant effect on accelerating rotarod performance (Fig. 2A). Despite the fact that exercise on a running wheel is superficially similar to the testing paradigm of the accelerating rotarod, mice engaged in this form of exercise from a juvenile age did not improve performance on the rotarod in either wild-type or HD mice at 5 months of age (Fig. 2B; wheel running: F [1, 25] = 0.40, P = 0.72; 2-way ANOVA). At 5 months, an effect of the HD mutation on performance was observed (Fig. 2B; HD: F[1, 28] = 8.58, P < 0.01; 2-way ANOVA). These results are consistent with, and extend, the recent finding that wheel running starting at an adult age has no effect on progression of rotarod deficits measured from 15–20 weeks of age [14].

Bottom Line: We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age.These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment.However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK. anthony.hannan@florey.edu.au

ABSTRACT

Background: Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit.

Results: We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running.

Conclusion: These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.

Show MeSH
Related in: MedlinePlus