Fluoxetine affects hippocampal plasticity, apoptosis and depressive-like behavior of chronically isolated rats.
Plastic response and successful adaptation to stress are of particular importance in the hippocampus, where chronic stress may cause cell death instead of neural remodeling. Structural modifications that occur both in the brain of depressed patients and animal stress models may be reversed by antidepressants. Since morphological changes induced by stress and/or antidepressants could be mediated by presynaptically located proteins, determining the levels of these proteins may be a useful way to identify molecular changes associated with synaptic plasticity. In this study we analyzed the effects of chronic (six-week) social isolation and long-term (three-week) fluoxetine treatment on molecular markers of plasticity and apoptosis in the hippocampus of Wistar rats. Compartmental redistribution of NFκB transcription factor involved in the regulation of plasticity and apoptosis was also examined. To establish whether social isolation is able to evoke behavioral-like effects, which might be related to the observed molecular changes, we performed the forced swimming test. The results show that synaptosomal polysialic neural cell adhesion molecule (PSA-NCAM), a molecular plasticity marker, was increased in the hippocampus of chronically isolated rats, while subsequent treatment with fluoxetine set it at the control level. In addition, analysis of cytoplasm/mitochondria redistribution of apoptotic proteins Bax and Bcl-2 after exposure to chronic isolation stress, revealed an increase in Bcl-2 protein expression in both compartments, while fluoxetine enhanced the effect of stress only in the mitochondria. The observed alterations at the molecular level were accompanied by normalization of stress-induced behavioral changes by fluoxetine.
Department of Biochemistry, Institute for Biological Research Siniša Stanković, University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia. djordjevica@ibiss.bg.ac.rs
Ana
A
Djordjevic
Jelena
J
Djordjevic
Ivana
I
Elaković
Miroslav
M
Adzic
Gordana
G
Matić
Marija B
MB
Radojcic
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000473:pathology* / Q000523:psychology; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012934:Social Isolation / Q000523:psychology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D005473:Fluoxetine