title: Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex.
abstract: The prefrontal cortex is the brain region sensitive to detrimental effects of stress and even mild stress can rapidly impair its function. Aside from initiating proadaptive neuroplastic changes in the prefrontal cortex, chronic stress may also increase vulnerability of cortical neurons to apoptosis. Understanding the mechanism of plasticity and apoptotic processes is of immense importance for therapy of stress-related psychiatric disorders. In this study we tested whether molecular alterations in the prefrontal cortex, which occurred upon chronic social isolation, could be influenced by a prolonged fluoxetine treatment. We analyzed the expression of synaptic plasticity and apoptotic molecular markers in the prefrontal cortex of young-adult male Wistar rats exposed to 6-week social isolation with and without fluoxetine treatment during the last 3 weeks. Compartmental redistribution of NFκB transcription factor, involved in regulation of plasticity and apoptosis, was also examined. The level of synaptosomal polysialic neural cell adhesion molecule (PSA-NCAM) was increased in the prefrontal cortex of isolated rats as compared to untreated controls. Treatment with fluoxetine reduced the PSA-NCAM level only in isolated animals. In addition, mitochondrial Bax protein was elevated by chronic social isolation, while fluoxetine failed to abolish this effect. In spite of elevated Bcl-2 in the mitochondria, the calculated Bax/Bcl-2 ratio and concomitant absence of NFκB activation pointed to initiation of apoptotic signaling in the prefrontal cortex. The results imply that fluoxetine influences plasticity in the prefrontal cortex of chronically isolated rats and fails to prevent stress-induced initiation of apoptosis in this brain structure.
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia. djordjevica@ibiss.bg.ac.rs
authors.forename: Ana
authors.initials: A
authors.lastname: Djordjevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.forename: Ivana
authors.initials: I
authors.lastname: Elaković
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
authors.forename: Gordana
authors.initials: G
authors.lastname: Matić
authors.forename: Marija B
authors.initials: MB
authors.lastname: Radojcic
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism; D013315:Stress, Psychological; D013574:Synaptosomes / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; C494826:BAX protein, human; D039842:Neural Cell Adhesion Molecule L1; D019253:Proto-Oncogene Proteins c-bcl-2; D050765:Qa-SNARE Proteins; D012794:Sialic Acids; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; C103469:polysialyl neural cell adhesion molecule; D005473:Fluoxetine