Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats
Само за регистроване кориснике
2013
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior. The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals. FLU was administrated to female and male naive or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior. The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way. In contrast, in both genders CPSI increased the nuclear levels of GR and pGR...246 but decreased CORT and mRNA levels of GR and BDNF. Concomitant FLU normalized the depressive-like behavior and altered the nuclear pGR232-Cdk5 signaling in a gender-specific manner. In both females and males, FLU reversed the nuclear levels of GR and pGR246 without affecting CORT and GR mRNA levels. In contrast, FLU exhibited gender-specific effect on BDNF mRNA in CPSI animals, by increasing it in females, but not in males. In spite of normalization the total nuclear GR level upon FLU treatment in both gender, down-regulation of GR mRNA is possibly maintained through prevalence of pGR232 isoform only in males. The gender-specific alterations of pGR232-Cdk5 signaling and BDNF gene expression in HIPPO and normalization of depressive-like behavior upon FLU treatment distinguishes this signaling pathway as potential future antidepressant target for gender-specific therapy of stress related mood disorders. (C) 2013 Elsevier Ltd. All rights reserved.
Кључне речи:
Fluoxetine / Glucocorticoid receptor phosphorylation / Chronic stress / Gender / HippocampusИзвор:
Neuropharmacology, 2013, 70, 100-111Финансирање / пројекти:
- Дефинисање кластера молекулских биомаркера за побољшану дијагностику и терапију поремећаја расположења (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41029)
DOI: 10.1016/j.neuropharm.2012.12.012
ISSN: 0028-3908; 1873-7064
PubMed: 23353902
WoS: 000319637600011
Scopus: 2-s2.0-84877006351
Институција/група
VinčaTY - JOUR AU - Mitić, Miloš AU - Simić, Iva AU - Đorđević, Jelena D. AU - Adžić, Miroslav AU - Radojčić, Marija PY - 2013 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5523 AB - Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior. The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals. FLU was administrated to female and male naive or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior. The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way. In contrast, in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF. Concomitant FLU normalized the depressive-like behavior and altered the nuclear pGR232-Cdk5 signaling in a gender-specific manner. In both females and males, FLU reversed the nuclear levels of GR and pGR246 without affecting CORT and GR mRNA levels. In contrast, FLU exhibited gender-specific effect on BDNF mRNA in CPSI animals, by increasing it in females, but not in males. In spite of normalization the total nuclear GR level upon FLU treatment in both gender, down-regulation of GR mRNA is possibly maintained through prevalence of pGR232 isoform only in males. The gender-specific alterations of pGR232-Cdk5 signaling and BDNF gene expression in HIPPO and normalization of depressive-like behavior upon FLU treatment distinguishes this signaling pathway as potential future antidepressant target for gender-specific therapy of stress related mood disorders. (C) 2013 Elsevier Ltd. All rights reserved. T2 - Neuropharmacology T1 - Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats VL - 70 SP - 100 EP - 111 DO - 10.1016/j.neuropharm.2012.12.012 ER -
@article{ author = "Mitić, Miloš and Simić, Iva and Đorđević, Jelena D. and Adžić, Miroslav and Radojčić, Marija", year = "2013", abstract = "Chronic psychosocial isolation stress (CPSI) modulates glucocorticoid receptor (GR) functioning in Wistar male rat hippocampus (HIPPO) through alteration of nuclear GR phosphorylation and its upstream kinases signaling, which parallels animal depressive-like behavior. The current study investigated potential gender specificities regarding the effect of chronic therapy by an antidepressant fluoxetine (FLU) on GR signaling in HIPPO and depressive-like behavior in CPSI animals. FLU was administrated to female and male naive or CPSI rats for 21 days and GR protein, its phosphorylation status and upstream kinases, as well as GR and BDNF mRNA were followed in HIPPO together with animal serum corticosterone (CORT) and depressive-like behavior. The results showed that CPSI increased immobility in males versus hyperactivity in females and disrupted nuclear pGR232-Cdk5 pathway and JNK signaling in a gender-specific way. In contrast, in both genders CPSI increased the nuclear levels of GR and pGR246 but decreased CORT and mRNA levels of GR and BDNF. Concomitant FLU normalized the depressive-like behavior and altered the nuclear pGR232-Cdk5 signaling in a gender-specific manner. In both females and males, FLU reversed the nuclear levels of GR and pGR246 without affecting CORT and GR mRNA levels. In contrast, FLU exhibited gender-specific effect on BDNF mRNA in CPSI animals, by increasing it in females, but not in males. In spite of normalization the total nuclear GR level upon FLU treatment in both gender, down-regulation of GR mRNA is possibly maintained through prevalence of pGR232 isoform only in males. The gender-specific alterations of pGR232-Cdk5 signaling and BDNF gene expression in HIPPO and normalization of depressive-like behavior upon FLU treatment distinguishes this signaling pathway as potential future antidepressant target for gender-specific therapy of stress related mood disorders. (C) 2013 Elsevier Ltd. All rights reserved.", journal = "Neuropharmacology", title = "Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats", volume = "70", pages = "100-111", doi = "10.1016/j.neuropharm.2012.12.012" }
Mitić, M., Simić, I., Đorđević, J. D., Adžić, M.,& Radojčić, M.. (2013). Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats. in Neuropharmacology, 70, 100-111. https://doi.org/10.1016/j.neuropharm.2012.12.012
Mitić M, Simić I, Đorđević JD, Adžić M, Radojčić M. Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats. in Neuropharmacology. 2013;70:100-111. doi:10.1016/j.neuropharm.2012.12.012 .
Mitić, Miloš, Simić, Iva, Đorđević, Jelena D., Adžić, Miroslav, Radojčić, Marija, "Gender-specific effects of fluoxetine on hippocampal glucocorticoid receptor phosphorylation and behavior in chronically stressed rats" in Neuropharmacology, 70 (2013):100-111, https://doi.org/10.1016/j.neuropharm.2012.12.012 . .