Therapeutic effects of clenbuterol in a murine model of amyotrophic lateral sclerosis

Teng, Yang D.; Choi, Howard; Huang, Weijie; Onario, Renna C.; Frontera, Walter R.; Snyder, Evan Y.; Sabharwal, Sunil

doi:10.1016/j.neulet.2005.12.007

Cited by 35 publications

(21 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies in animal models have demonstrated beneficial effects of treatment with β 2 -agonists in conditions of muscular dystrophy, disuse, aging, denervation or amyotrophic lateral sclerosis [27], [28], [29], [30], [31], [32].…”

Section: Discussionmentioning

confidence: 99%

Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle

et al. 2014

View full text Add to dashboard Cite

Clenbuterol, a β2-agonist, induces skeletal muscle hypertrophy and a shift from slow-oxidative to fast-glycolytic muscle fiber type profile. However, the cellular mechanisms of the effects of chronic clenbuterol administration on skeletal muscle are not completely understood. As the intracellular Ca2+ concentration must be finely regulated in many cellular processes, the aim of this study was to investigate the effects of chronic clenbuterol treatment on force, fatigue, intracellular calcium (Ca2+) homeostasis and Ca2+-dependent proteolysis in fast-twitch skeletal muscles (the extensor digitorum longus, EDL, muscle), as they are more sensitive to clenbuterol-induced hypertrophy. Male Wistar rats were chronically treated with 4 mg.kg−1 clenbuterol or saline vehicle (controls) for 21 days. Confocal microscopy was used to evaluate sarcoplasmic reticulum Ca2+ load, Ca2+ -transient amplitude and Ca2+ spark properties. EDL muscles from clenbuterol-treated animals displayed hypertrophy, a shift from slow to fast fiber type profile and increased absolute force, while the relative force remained unchanged and resistance to fatigue decreased compared to control muscles from rats treated with saline vehicle. Compared to control animals, clenbuterol treatment decreased Ca2+-transient amplitude, Ca2+ spark amplitude and frequency and the sarcoplasmic reticulum Ca2+ load was markedly reduced. Conversely, calpain activity was increased by clenbuterol chronic treatment. These results indicate that chronic treatment with clenbuterol impairs Ca2+ homeostasis and this could contribute to the remodeling and functional impairment of fast-twitch skeletal muscle.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Using motor neuron degeneration (mnd) mice which exhibit lysosomal accumulation of lipofuscin-like material associated with a progressive loss of motor function and strength, Zeman et al (482) reported that clenbuterol treatment (ϳ1 mg⅐kg Ϫ1 ⅐day Ϫ1 in the drinking water) enhanced regeneration of motor neuron axons, opposed the development of motor deficits, and attenuated the decreases in grip strength and muscle mass. In G93A-SOD1 mice, a transgenic murine model of familial ALS, clenbuterol administration (1.5 mg⅐kg Ϫ1 ⅐day Ϫ1 ip) delayed onset of hindlimb weakness, as measured by performance on a rotarod, and slowed disease progression (434). A pilot trial using clenbuterol for ALS has been reported in Italy (417).…”

Section: Motor Neuron Disease: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease

Lynch¹,

Ryall²

2008

Physiological Reviews

363

356

View full text Add to dashboard Cite

The importance of beta-adrenergic signaling in the heart has been well documented, but it is only more recently that we have begun to understand the importance of this signaling pathway in skeletal muscle. There is considerable evidence regarding the stimulation of the beta-adrenergic system with beta-adrenoceptor agonists (beta-agonists). Although traditionally used for treating bronchospasm, it became apparent that some beta-agonists could increase skeletal muscle mass and decrease body fat. These so-called "repartitioning effects" proved desirable for the livestock industry trying to improve feed efficiency and meat quality. Studying beta-agonist effects on skeletal muscle has identified potential therapeutic applications for muscle wasting conditions such as sarcopenia, cancer cachexia, denervation, and neuromuscular diseases, aiming to attenuate (or potentially reverse) the muscle wasting and associated muscle weakness, and to enhance muscle growth and repair after injury. Some undesirable cardiovascular side effects of beta-agonists have so far limited their therapeutic potential. This review describes the physiological significance of beta-adrenergic signaling in skeletal muscle and examines the effects of beta-agonists on skeletal muscle structure and function. In addition, we examine the proposed beneficial effects of beta-agonist administration on skeletal muscle along with some of the less desirable cardiovascular effects. Understanding beta-adrenergic signaling in skeletal muscle is important for identifying new therapeutic targets and identifying novel approaches to attenuate the muscle wasting concomitant with many diseases.

show abstract

“…Some anabolic substances are known to prevent extended body weight loss and muscle wasting in different disorders (Dudgeon et al, 2006;Koopman et al, 2009;Shahidi, 2001). Among these substances, clenbuterol, a b 2 -adrenergic agonist generally used to treat asthma (Anderson and Wilkins, 1977), has been reported to stimulate muscle growth (Carter et al, 1991;Choo et al, 1992;Lynch et al, 1999;MacLennan and Edwards, 1989) and to prevent muscle atrophy in dystrophic, hindlimb unloaded, or nerve-transected models (Agbenyega et al, 1995;Herrera et al, 2001;Teng et al, 2006;Zeman et al, 2000). Interestingly, we recently found that a significant decrease in testosterone level occurs shortly after spinal cord transection, suggesting a role for this hormone in the rapid muscle mass changes seen after SCI (Rouleau et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Effects of Co-Administration of Clenbuterol and Testosterone Propionate on Skeletal Muscle in Paraplegic Mice

Ung

Rouleau

Guertin

2010

Journal of Neurotrauma

View full text Add to dashboard Cite

Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.

show abstract

Therapeutic effects of clenbuterol in a murine model of amyotrophic lateral sclerosis

Cited by 35 publications

References 18 publications

Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle

Effects of Chronic Administration of Clenbuterol on Contractile Properties and Calcium Homeostasis in Rat Extensor Digitorum Longus Muscle

Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease

Effects of Co-Administration of Clenbuterol and Testosterone Propionate on Skeletal Muscle in Paraplegic Mice

Contact Info

Product

Resources

About