title: Chronic stress-induced changes in the rat brain: role of sex differences and effects of long-term tianeptine treatment.
abstract: Growing evidence suggests neuroplasticity changes are pivotal in both the occurrence and treatment of affective disorders. Abnormal expression and/or phosphorylation of numerous plasticity-related proteins have been observed in depression, while prolonged antidepressant treatment has been associated with the attenuation of stress-mediated effects on dendritic remodeling and adult hippocampal neurogenesis in experimental animals. This study explores the neurobiological adaptations induced by chronic stress and/or long-term tianeptine treatment. Male and female rats were studied to determine the potential contributory role of sex differences on stress-induced pathology and antidepressant-mediated actions. Our results confirm chronic stress-induced HPA axis disturbance and neuroplasticity impairment in both sexes (i.e. reduced CREB phosphorylation and hippocampal BrdU labeling). Commonly ensuing neurobiological alterations were accompanied by unique sex-specific adaptations. When the antidepressant tianeptine was administered, HPA axis hyperactivity was attenuated and specific neuronal defects were ameliorated in both sexes. These findings provide novel insight into sex-related influences on the neurobiological substrates mediating chronic stress-induced actions on neuroplasticity and the mechanisms underlying tianeptine-mediated therapeutic effects.
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Psychiatry, The Netherlands; Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
authors.forename: Sjoukje D
authors.initials: SD
authors.lastname: Kuipers
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Psychiatry, The Netherlands; Department of Molecular Neurobiology, Centre for Behaviour and Neurosciences, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands; Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. Electronic address: atrentani@yahoo.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trentani
authors.affiliation: Department of Molecular Neurobiology, Centre for Behaviour and Neurosciences, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
authors.forename: Eddy A
authors.initials: EA
authors.lastname: van der Zee
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Psychiatry, The Netherlands.
authors.forename: Johan A
authors.initials: JA
authors.lastname: den Boer
mesh_terms: D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004597:Electroshock / Q000009:adverse effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D013841:Thiazepines / Q000627:therapeutic use*; D013950:Thymus Gland / Q000473:pathology; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D016760:Proto-Oncogene Proteins c-fos; D013841:Thiazepines; C050504:tianeptine; D050882:CREB-Binding Protein; D001973:Bromodeoxyuridine; D003345:Corticosterone
keywords: BrdU; CREB phosphorylation; Chronic stress; FOS expression; Sex differences; Tianeptine