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ARTICLE, Behavioral/Systems

Circulating Insulin-Like Growth Factor I Mediates the Protective Effects of Physical Exercise against Brain Insults of Different Etiology and Anatomy

Eva Carro, Jose Luis Trejo, Svetlana Busiguina and Ignacio Torres-Aleman
Journal of Neuroscience 1 August 2001, 21 (15) 5678-5684; DOI: https://doi.org/10.1523/JNEUROSCI.21-15-05678.2001
Eva Carro
1Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientı́ficas, 28002 Madrid, Spain
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Jose Luis Trejo
1Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientı́ficas, 28002 Madrid, Spain
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Svetlana Busiguina
1Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientı́ficas, 28002 Madrid, Spain
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Ignacio Torres-Aleman
1Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientı́ficas, 28002 Madrid, Spain
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Abstract

Physical exercise ameliorates age-related neuronal loss and is currently recommended as a therapeutical aid in several neurodegenerative diseases. However, evidence is still lacking to firmly establish whether exercise constitutes a practical neuroprotective strategy. We now show that exercise provides a remarkable protection against brain insults of different etiology and anatomy. Laboratory rodents were submitted to treadmill running (1 km/d) either before or after neurotoxin insult of the hippocampus (domoic acid) or the brainstem (3-acetylpyridine) or along progression of inherited neurodegeneration affecting the cerebellum (Purkinje cell degeneration). In all cases, animals show recovery of behavioral performance compared with sedentary ones, i.e., intact spatial memory in hippocampal-injured mice, and normal or near to normal motor coordination in brainstem- and cerebellum-damaged animals. Furthermore, exercise blocked neuronal impairment or loss in all types of injuries. Because circulating insulin-like growth factor I (IGF-I), a potent neurotrophic hormone, mediates many of the effects of exercise on the brain, we determined whether neuroprotection by exercise is mediated by IGF-I. Indeed, subcutaneous administration of a blocking anti-IGF-I antibody to exercising animals to inhibit exercise-induced brain uptake of IGF-I abrogates the protective effects of exercise in all types of lesions; antibody-treated animals showed sedentary-like brain damage. These results indicate that exercise prevents and protects from brain damage through increased uptake of circulating IGF-I by the brain. The practice of physical exercise is thus strongly recommended as a preventive measure against neuronal demise. These findings also support the use of IGF-I as a therapeutical aid in brain diseases coursing with either acute or progressive neuronal death.

  • neurodegeneration
  • physical exercise
  • insulin-like growth factor I
  • neurotoxins
  • Purkinje cell degeneration
  • neuroprotection
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The Journal of Neuroscience: 21 (15)
Journal of Neuroscience
Vol. 21, Issue 15
1 Aug 2001
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Circulating Insulin-Like Growth Factor I Mediates the Protective Effects of Physical Exercise against Brain Insults of Different Etiology and Anatomy
Eva Carro, Jose Luis Trejo, Svetlana Busiguina, Ignacio Torres-Aleman
Journal of Neuroscience 1 August 2001, 21 (15) 5678-5684; DOI: 10.1523/JNEUROSCI.21-15-05678.2001

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Circulating Insulin-Like Growth Factor I Mediates the Protective Effects of Physical Exercise against Brain Insults of Different Etiology and Anatomy
Eva Carro, Jose Luis Trejo, Svetlana Busiguina, Ignacio Torres-Aleman
Journal of Neuroscience 1 August 2001, 21 (15) 5678-5684; DOI: 10.1523/JNEUROSCI.21-15-05678.2001
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Keywords

  • neurodegeneration
  • physical exercise
  • insulin-like growth factor I
  • neurotoxins
  • Purkinje cell degeneration
  • neuroprotection

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