{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:25:14Z","timestamp":1781108714741,"version":"3.54.1"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,6,24]]},"abstract":"<jats:p>\n                    Recent microarray studies with stringent validating criteria identified Bcl-2-associated athanogene (\n                    <jats:italic>BAG1<\/jats:italic>\n                    ) as a target for the actions of medications that are mainstays in the treatment of bipolar disorder (BPD).\n                    <jats:italic>BAG1<\/jats:italic>\n                    is a Hsp70\/Hsc70-regulating cochaperone that also interacts with glucocorticoid receptors (GRs) and attenuates their nuclear trafficking and function. Notably, glucocorticoids are one of the few agents capable of triggering both depressive and manic episodes in patients with BPD. As a nexus for the actions of glucocorticoids and bipolar medications, we hypothesized that the level of\n                    <jats:italic>BAG1<\/jats:italic>\n                    expression would play a pivotal role in regulating affective-like behaviors. This hypothesis was investigated in neuron-selective\n                    <jats:italic>BAG1<\/jats:italic>\n                    transgenic (TG) mice and\n                    <jats:italic>BAG1<\/jats:italic>\n                    heterozygous knockout (+\/\u2212) mice. On mania-related tests,\n                    <jats:italic>BAG1<\/jats:italic>\n                    TG mice recovered much faster than wild-type (WT) mice in the amphetamine-induced hyperlocomotion test and displayed a clear resistance to cocaine-induced behavioral sensitization. In contrast,\n                    <jats:italic>BAG1<\/jats:italic>\n                    +\/\u2212 mice displayed an enhanced response to cocaine-induced behavioral sensitization. The\n                    <jats:italic>BAG1<\/jats:italic>\n                    TG mice showed less anxious-like behavior on the elevated plus maze test and had higher spontaneous recovery rates from helplessness behavior compared with WT mice. In contrast, fewer\n                    <jats:italic>BAG1<\/jats:italic>\n                    +\/\u2212 mice recovered from helplessness behavior compared with their WT controls.\n                    <jats:italic>BAG1<\/jats:italic>\n                    TG mice also exhibited specific alterations of hippocampal proteins known to regulate GR function, including Hsp70 and FKBP51. These data suggest that\n                    <jats:italic>BAG1<\/jats:italic>\n                    plays a key role in affective resilience and in regulating recovery from both manic-like and depression-like behavioral impairments.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0803736105","type":"journal-article","created":{"date-parts":[[2008,6,18]],"date-time":"2008-06-18T21:35:49Z","timestamp":1213824949000},"page":"8766-8771","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":60,"title":["<i>BAG1<\/i>\n                    plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments"],"prefix":"10.1073","volume":"105","author":[{"given":"Sungho","family":"Maeng","sequence":"first","affiliation":[{"name":"*Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua G.","family":"Hunsberger","sequence":"additional","affiliation":[{"name":"*Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Pearson","sequence":"additional","affiliation":[{"name":"*Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixiong","family":"Yuan","sequence":"additional","affiliation":[{"name":"*Laboratory of Molecular 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20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"McCammon","sequence":"additional","affiliation":[{"name":"*Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Schloesser","sequence":"additional","affiliation":[{"name":"*Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rulun","family":"Zhou","sequence":"additional","affiliation":[{"name":"*Laboratory of Molecular Pathophysiology and Experimental Therapeutics, Mood and Anxiety 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