title: Differences in FKBP51 regulation following chronic social defeat stress correlate with individual stress sensitivity: influence of paroxetine treatment.
abstract: Various clinical studies have identified FK506-binding protein 51 (FKBP51) as a target gene involved in the development of psychiatric disorders such as depression. Furthermore, FKBP51 has been shown to affect glucocorticoid receptor signaling by sensitivity modulation and it is implicated in stress reactivity as well as in molecular mechanisms of stress vulnerability and resilience. We investigated the physiological, behavioral, and neuroendocrine parameters in an established chronic stress model both directly after stress and after a recovery period of 3 weeks and also studied the efficacy of paroxetine in this model. We then examined FKBP51 mRNA levels in the dorsal and ventral part of the hippocampus and correlated the expression to behavioral and endocrine parameters. We show robust chronic stress effects in physiological, behavioral, and neuroendocrine parameters, which were only slightly affected by paroxetine treatment. On the contrary, paroxetine led to a disruption of the neuroendocrine system. FKBP51 expression was significantly increased directly after the stress period and correlated with behavioral and neuroendocrine parameters. Taken together, we were able to further elucidate the role of FKBP51 in the mechanisms of stress resilience and vulnerability, especially with respect to behavioral and neuroendocrine parameters. These findings strongly support the concept of FKBP51 as a marker for glucocorticoid receptor sensitivity and its involvement in the development of psychiatric disorders.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany. kwagner@mpipsykl.mpg.de
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Wagner
authors.forename: Daria
authors.initials: D
authors.lastname: Marinescu
authors.forename: Jakob
authors.initials: J
authors.lastname: Hartmann
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Christiana
authors.initials: C
authors.lastname: Labermaier
authors.forename: Sebastian H
authors.initials: SH
authors.lastname: Scharf
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebl
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017374:Paroxetine / Q000627:therapeutic use*; D012919:Social Behavior; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D016896:Treatment Outcome; D000099159:Tacrolimus Binding Protein 5
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5