Chronic antidepressant treatments increase basic fibroblast growth factor and fibroblast growth factor-binding protein in neurons.
One of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic connections and plasticity in the hippocampus and cerebral cortex. Fibroblast growth factor 2 (FGF2) is a growth factor essential for the proper formation of synaptic connections in the cerebral cortex, maturation and survival of catecholamine neurons, and neurogenesis. In this report, we attempted to establish a correlation between antidepressant treatments and FGF2 expression in the cerebral cortex and hippocampus, two brain areas relevant for depression. Desipramine (DMI, 10mg/kg) or fluoxetine (FLU, 5mg/kg) was injected acutely (single injection) or chronically (daily injection for two weeks) in adult rats. Chronic, but not acute, antidepressant treatments increase FGF2 immunoreactivity in neurons of the cerebral cortex and in both astrocytes and neurons of the hippocampus. FGF2 immunoreactivity in the cortex was increased mainly in the cytoplasm of neurons of layer V. Western blot analyses of nuclear and cytosolic extracts from the cortex revealed that both antidepressants increase FGF2 isoforms in the cytosolic extracts and decrease accumulation of FGF2 immunoreactivity in the nucleus. To characterize the anatomical and cellular specificity of antidepressants, we examined FGF-binding protein (FBP), a secreted protein that acts as an extracellular chaperone for FGF2 and enhances its activity. DMI and FLU increased FBP immunoreactivity in both cortical and hippocampal neurons. Our data suggest that FGF2 and FBP may participate in the plastic responses underlying the clinical efficacy of antidepressants.
Bachis
Alessia
A
Department of Neuroscience, Georgetown University Medical Center, EP04, New Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USA.
Mallei
Alessandra
A
Cruz
Maria Idalia
MI
Wellstein
Anton
A
Mocchetti
Italo
I
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000378:metabolism*; D016666:Fluvoxamine / Q000494:pharmacology; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D003891:Desipramine; D016222:Fibroblast Growth Factor 2; D016666:Fluvoxamine; D017468:Receptors, Fibroblast Growth Factor; D017367:Selective Serotonin Reuptake Inhibitors