Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy

Jennifer Manning, Rebecca Kulbida, Prerana Rai, Lindsay Jensen, Judith Bouma, Sanjay Singh, D. O'Malley, Deniz M. Yilmazer-Hanke

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg-1 daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.

Original languageEnglish
Pages (from-to)1370-1386
Number of pages17
JournalExperimental Physiology
Volume99
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Inbred mdx Mouse
Amitriptyline
Duchenne Muscular Dystrophy
Depression
Inflammation
Muscles
Amygdala
Dystrophin
Skeletal Muscle
Cytokines
Interleukin-6
Hippocampus
Anxiety
Hindlimb Suspension
Therapeutics
Forelimb
Muscular Dystrophies
Tricyclic Antidepressive Agents
Anti-Anxiety Agents
Mesencephalon

All Science Journal Classification (ASJC) codes

  • Physiology
  • Medicine(all)

Cite this

Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy. / Manning, Jennifer; Kulbida, Rebecca; Rai, Prerana; Jensen, Lindsay; Bouma, Judith; Singh, Sanjay; O'Malley, D.; Yilmazer-Hanke, Deniz M.

In: Experimental Physiology, Vol. 99, No. 10, 2014, p. 1370-1386.

Research output: Contribution to journalArticle

Manning, Jennifer ; Kulbida, Rebecca ; Rai, Prerana ; Jensen, Lindsay ; Bouma, Judith ; Singh, Sanjay ; O'Malley, D. ; Yilmazer-Hanke, Deniz M. / Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy. In: Experimental Physiology. 2014 ; Vol. 99, No. 10. pp. 1370-1386.
@article{2af2836060224b70ba289112d0ee914a,
title = "Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy",
abstract = "Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg-1 daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.",
author = "Jennifer Manning and Rebecca Kulbida and Prerana Rai and Lindsay Jensen and Judith Bouma and Sanjay Singh and D. O'Malley and Yilmazer-Hanke, {Deniz M.}",
year = "2014",
doi = "10.1113/expphysiol.2014.079475",
language = "English",
volume = "99",
pages = "1370--1386",
journal = "Experimental Physiology",
issn = "0958-0670",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy

AU - Manning, Jennifer

AU - Kulbida, Rebecca

AU - Rai, Prerana

AU - Jensen, Lindsay

AU - Bouma, Judith

AU - Singh, Sanjay

AU - O'Malley, D.

AU - Yilmazer-Hanke, Deniz M.

PY - 2014

Y1 - 2014

N2 - Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg-1 daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.

AB - Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg-1 daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.

UR - http://www.scopus.com/inward/record.url?scp=84908478691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908478691&partnerID=8YFLogxK

U2 - 10.1113/expphysiol.2014.079475

DO - 10.1113/expphysiol.2014.079475

M3 - Article

C2 - 24972834

AN - SCOPUS:84908478691

VL - 99

SP - 1370

EP - 1386

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 10

ER -