BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. Export

@article{citeulike:2910563, abstract = {Recent microarray studies with stringent validating criteria identified Bcl-2-associated athanogene (BAG1) as a target for the actions of medications that are mainstays in the treatment of bipolar disorder (BPD). BAG1 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 BAG1 expression would play a pivotal role in regulating affective-like behaviors. This hypothesis was investigated in neuron-selective BAG1 transgenic (TG) mice and BAG1 heterozygous knockout (+/-) mice. On mania-related tests, BAG1 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, BAG1+/- mice displayed an enhanced response to cocaine-induced behavioral sensitization. The BAG1 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 BAG1+/- mice recovered from helplessness behavior compared with their WT controls. BAG1 TG mice also exhibited specific alterations of hippocampal proteins known to regulate GR function, including Hsp70 and FKBP51. These data suggest that BAG1 plays a key role in affective resilience and in regulating recovery from both manic-like and depression-like behavioral impairments.}, address = {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;}, author = {Maeng, Sungho and Hunsberger, Joshua G G. and Pearson, Brandon and Yuan, Peixiong and Wang, Yun and Wei, Yanling and McCammon, Joseph and Schloesser, Robert J J. and Zhou, Rulun and Du, Jing and Chen, Guang and McEwen, Bruce and Reed, John C C. and Manji, Husseini K K.}, citeulike-article-id = {2910563}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0803736105}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18562287}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18562287}, day = {18}, doi = {10.1073/pnas.0803736105}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, month = {June}, posted-at = {2008-06-20 14:59:05}, priority = {2}, title = {BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments.}, url = {http://dx.doi.org/10.1073/pnas.0803736105}, year = {2008} }

TY - JOUR ID - citeulike:2910563 L3 - citeulike-article-id:2910563 N2 - Recent microarray studies with stringent validating criteria identified Bcl-2-associated athanogene (BAG1) as a target for the actions of medications that are mainstays in the treatment of bipolar disorder (BPD). BAG1 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 BAG1 expression would play a pivotal role in regulating affective-like behaviors. This hypothesis was investigated in neuron-selective BAG1 transgenic (TG) mice and BAG1 heterozygous knockout (+/-) mice. On mania-related tests, BAG1 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, BAG1+/- mice displayed an enhanced response to cocaine-induced behavioral sensitization. The BAG1 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 BAG1+/- mice recovered from helplessness behavior compared with their WT controls. BAG1 TG mice also exhibited specific alterations of hippocampal proteins known to regulate GR function, including Hsp70 and FKBP51. These data suggest that BAG1 plays a key role in affective resilience and in regulating recovery from both manic-like and depression-like behavioral impairments. JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 AD - 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; TI - BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. AU - Maeng, Sungho AU - Hunsberger, Joshua G AU - Pearson, Brandon AU - Yuan, Peixiong AU - Wang, Yun AU - Wei, Yanling AU - McCammon, Joseph AU - Schloesser, Robert J AU - Zhou, Rulun AU - Du, Jing AU - Chen, Guang AU - McEwen, Bruce AU - Reed, John C AU - Manji, Husseini K PY - 2008/06/18/ UR - http://dx.doi.org/10.1073/pnas.0803736105 ER -