Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency

Michael J. Zigmond, Judy L. Cameron, Rehana K. Leak, Karoly Mirnics, Vivienne A. Russell, Richard J. Smeyne, Amanda D. Smith

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

We are testing the hypothesis that exercise is neuroprotective in animal models of the dopamine (DA) deficiency in Parkinson's disease. Our studies include mice or rats provided access to a running wheel and subsequently treated with MPTP (mice) or 6-hydroxydopamine (rats) and monkeys provided access to a treadmill and subsequently treated with MPTP. Typically, the exercise occurs for 3 months prior to the toxin treatment and often for 1-2 months thereafter. Our findings indicate that exercise reduces the behavioral impairments elicited by the dopaminergic neurotoxins as well as the loss of DA neurons as assessed by PET imaging and biochemical or histochemical assessment of tissue samples. Our studies are focused on one of several possible explanations for the beneficial effects of exercise: an exercise-induced increase in the expression of neurotrophic factors, particularly GDNF. Our observations indicate that GDNF can reduce the vulnerability of DA neurons, in part due to the activation of key intracellular cascades. We also find that mild cellular stress itself can provide protection against more intensive stress, a form of preconditioning. We conclude that dopamine neurons have the capacity to respond to intracellular and extracellular signals by triggering endogenous neuroprotective mechanisms. This raises the possibility that some individuals with Parkinson's disease suffer from a reduction of these neuroprotective mechanisms, and that treatments that boost these mechanisms - including exercise - may provide therapeutic benefit.

Original languageEnglish (US)
Pages (from-to)S42-S45
JournalParkinsonism and Related Disorders
Volume15
Issue numberSUPPL. 3
DOIs
StatePublished - Dec 1 2009

Fingerprint

Dopaminergic Neurons
Glial Cell Line-Derived Neurotrophic Factor
Dopamine
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Parkinson Disease
Oxidopamine
Nerve Growth Factors
Neurotoxins
Running
Haplorhini
Animal Models
Therapeutics

Keywords

  • Dopamine
  • Kinases
  • Mice
  • Monkeys
  • Rats
  • Striatum
  • Trophic factors

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Zigmond, M. J., Cameron, J. L., Leak, R. K., Mirnics, K., Russell, V. A., Smeyne, R. J., & Smith, A. D. (2009). Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. Parkinsonism and Related Disorders, 15(SUPPL. 3), S42-S45. https://doi.org/10.1016/S1353-8020(09)70778-3

Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. / Zigmond, Michael J.; Cameron, Judy L.; Leak, Rehana K.; Mirnics, Karoly; Russell, Vivienne A.; Smeyne, Richard J.; Smith, Amanda D.

In: Parkinsonism and Related Disorders, Vol. 15, No. SUPPL. 3, 01.12.2009, p. S42-S45.

Research output: Contribution to journalArticle

Zigmond, Michael J. ; Cameron, Judy L. ; Leak, Rehana K. ; Mirnics, Karoly ; Russell, Vivienne A. ; Smeyne, Richard J. ; Smith, Amanda D. / Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. In: Parkinsonism and Related Disorders. 2009 ; Vol. 15, No. SUPPL. 3. pp. S42-S45.
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