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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\n                    <jats:sup>G93A<\/jats:sup>\n                    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\n                    <jats:italic>vs<\/jats:italic>\n                    . 122 d) when compared to non\u2010stressed 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:\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    =0.746; females:\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    =0.707) and shorter survival times (males:\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    =0.680; females:\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    =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.\u2014Fidler, 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.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 4369\u20134377 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-190819","type":"journal-article","created":{"date-parts":[[2011,8,29]],"date-time":"2011-08-29T22:05:45Z","timestamp":1314655545000},"page":"4369-4377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Disease progression in a mouse model of amyotrophic lateral sclerosis: the influence of chronic stress and corticosterone"],"prefix":"10.1096","volume":"25","author":[{"given":"Jonathan A.","family":"Fidler","sequence":"first","affiliation":[{"name":"Genzyme Corporation  Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Treleaven","sequence":"additional","affiliation":[{"name":"Genzyme Corporation  Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Frakes","sequence":"additional","affiliation":[{"name":"Research Institute at Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"College of Medicine Integrated Biomedical Graduate Program, Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Tamsett","sequence":"additional","affiliation":[{"name":"Genzyme Corporation  Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"McCrate","sequence":"additional","affiliation":[{"name":"Research Institute at Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"College of Medicine Integrated Biomedical Graduate Program, Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng H.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Genzyme Corporation  Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamya S.","family":"Shihabuddin","sequence":"additional","affiliation":[{"name":"Genzyme Corporation  Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Kaspar","sequence":"additional","affiliation":[{"name":"Research Institute at Nationwide Children's Hospital  Columbus Ohio USA"},{"name":"College of Medicine Integrated Biomedical Graduate Program, Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Dodge","sequence":"additional","affiliation":[{"name":"Genzyme Corporation  Framingham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.8.1139"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/09638289309166002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1994.00540130027010"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh373"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000148649.17706.D9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.106"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb09546.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0350"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.040403.120816"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-7-3-284"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03349149"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.30.1.98"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91680-Y"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(01)00217-X"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5100-z"},{"key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3109\/17482960902822960","article-title":"Impaired glucose tolerance in patients with amyotrophic lateral sclerosis","volume":"11","author":"Pradat P. 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