Insulin-Like Growth Factor I Signaling for Brain Recovery and Exercise Ability in Brain Ischemic Rats

CHANG, HENG-CHIH1; YANG, YEA-RU2; WANG, PAULUS S.1; KUO, CHIA-HUA3; WANG, RAY-YAU2

Medicine & Science in Sports & Exercise:
doi: 10.1249/MSS.0b013e318223b5d9
Basic Sciences
Abstract

Purpose: Exercise increases neuron survival and plasticity in the adult brain by enhancing the uptake of insulin-like growth factor I (IGF-I). Exercise also reduces the infarct volume in the ischemic brain and improves motor function after such a brain insult. However, the underlying mechanisms are not fully known. The purpose of this study was to investigate the involvement of IGF-I signaling in neuroprotection after exercise.

Method: Rats were assigned to one of four groups: middle cerebral artery occlusion (MCAO) without exercise training (MC), MCAO with exercise training (ME), MCAO with IGF-I receptor inhibitor and without exercise training (MAg), and MCAO with IGF-I receptor inhibitor and exercise training (MEAg). Rats in the ME and MEAg groups underwent treadmill training for 14 d, and rats in the MC and MAg groups served as controls. After the final intervention, rats were sacrificed under anesthesia, and samples were collected from the affected motor cortex, striatum, and plasma.

Results: IGF-I and p-Aktser473 levels in the affected motor cortex and the striatum of the ME group were significantly higher than those in the MC group, with significant decreases in infarct volume and improvements in motor function. However, IGF-I receptor inhibitor eliminated these effects and decreased the exercise ability. The brain IGF-I signaling strongly correlated with exercise ability.

Conclusions: Exercise-enhanced IGF-I entrance into ischemic brain and IGF-I signaling was related to exercise-mediated neuroprotection. IGF-1 signaling also affected the ability to exercise after brain ischemia.

Author Information

1Department and Institute of Physiology, National Yang-Ming University, Taipei, TAIWAN; 2Department of Physical Therapy and Assistive Technology, National Yang-Ming University, Taipei, TAIWAN; and 3Graduate Institute of Exercise Science, Taipei Physical Education College, Taipei, TAIWAN

Address for correspondence: Ray-Yau Wang, Ph.D., P.T., Department of Physical Therapy and Assistive Technology, National Yang-Ming University,155, Section 2, Li-Nong Street, Taipei, Taiwan; E-mail: rywang@ym.edu.tw.

Submitted for publication January 2011.

Accepted for publication May 2011.

©2011The American College of Sports Medicine