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- W4211021305 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. PMID: 18562287 Funding information This work was supported by: Intramural NIH HHS, United States Grant ID: Z99 MH999999 NCI NIH HHS, United States Grant ID: CA-67329" @default.
- W4211021305 created "2022-02-13" @default.
- W4211021305 creator A5087594298 @default.
- W4211021305 date "2008-07-09" @default.
- W4211021305 modified "2023-09-27" @default.
- W4211021305 title "Faculty Opinions recommendation of BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments." @default.
- W4211021305 doi "https://doi.org/10.3410/f.1116532.572567" @default.
- W4211021305 hasPublicationYear "2008" @default.
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