Journal
FASEB JOURNAL
Volume 25, Issue 12, Pages 4369-4377Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.11-190819
Keywords
ALS; motor neuron disease; MND; glucocorticoid; allostasis; cacostasis
Categories
Funding
- U.S. National Institutes of Health [R01NS064492, RC2NS069476-01]
- ALS
- Muscular Dystrophy Association
Ask authors/readers for more resources
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron cell loss, muscular atrophy, and a shortened life span. Survival is highly variable, as some patients die within months, while others live for many years. Exposure to stress or the development of a nonoptimal stress response to disease might account for some of this variability. We show in the SOD1(G93A) mouse model of ALS that recurrent exposure to restraint stress led to an earlier onset of astrogliosis and microglial activation within the spinal cord, accelerated muscular weakness, and a significant decrease in median survival (105 vs. 122 d) when compared to non-stressed animals. Moreover, during normal disease course, ALS mice display a cacostatic stress response by developing an aberrant serum corticosterone circadian rhythm. Interestingly, we also found that higher corticosterone levels were significantly correlated with both an earlier onset of paralysis (males: r(2)=0.746; females: r(2)=0.707) and shorter survival times (males: r(2)=0.680; females: r(2)=0.552) in ALS mice. These results suggest that stress is capable of accelerating disease progression and that strategies that modulate glucocorticoid metabolism might be a viable treatment approach for ALS.-Fidler, J. A., Treleaven, C. M., Frakes, A., Tamsett, T. J., McCrate, M., Cheng, S. H., Shihabuddin, L. S., Kaspar, B. K., Dodge, J. C. Disease progression in a mouse model of amyotrophic lateral sclerosis: the influence of chronic stress and corticosterone. FASEB J. 25, 4369-4377 (2011). www.fasebj.org
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available