HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 106/6/2049    most recent 91505.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Caron, A. Z. Articles by Grenier, G. PubMed PubMed Citation Articles by Caron, A. Z. Articles by Grenier, G.

HIGHLIGHTED TOPIC
Regulation of Protein Metabolism in Exercise and Recovery

A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse

¹Department of Orthopaedic Surgery, ²Research Centre on Aging, ³Étienne-Lebel Clinical Research Centre, and ⁴Cellular Biology Program, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Submitted 19 November 2008 ; accepted in final form 30 March 2009

Skeletal muscle atrophy is a serious concern for patients afflicted by limb restriction due to surgery (e.g., arthrodesis), several articular pathologies (e.g., arthralgia), or simply following cast immobilization. To study the molecular events involved in this immobilization-induced debilitating condition, a convenient mouse model for atrophy is lacking. Here we provide a new immobilization procedure exploiting the normal flexion of the mouse hindlimb using a surgical staple to fix the ventral part of the foot to the distal part of the calf. Histological analysis revealed that our approach induced significant skeletal muscle atrophy by reducing the myofiber size of the tibialis anterior (TA) muscle by 36% compared with the untreated contralateral TA within a few days postimmobilization. Two molecular markers for atrophy, atrogin-1/muscle atrophy F-box (atrogin-1/MAFbx) and muscle ring finger 1 (MuRF-1) mRNAs, were significantly upregulated by 1.9- and 5.9-fold, respectively. Interestingly, our model also revealed the presence of an early inflammatory process during atrophy, characterized by the mRNA upregulation of TNF-, IL-1, and IL-6 (1.9-, 2.4-, and 3.4-fold, respectively) simultaneously with the upregulation of the common leukocyte marker CD45 (6.1-fold). Moreover, muscle rapidly recovered on remobilization, an event associated with significantly increased levels of uncoupling protein-3 and peroxisome proliferator-activated receptor coactivator-1 mRNA, key components of prooxidative muscle metabolism. This model offers unexpected new insights into the molecular events involved in immobilization atrophy.

disuse; inflammation; exhaustion; oxidative metabolism