Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.
Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP) of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d) that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity.
Alme
Maria Nordheim
MN
Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
Wibrand
Karin
K
Dagestad
Grethe
G
Bramham
Clive R
CR
D020727:ADP-Ribosylation Factors / Q000235:genetics; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002097:C-Reactive Protein / Q000235:genetics; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004334:Drug Administration Schedule; D004351:Drug Resistance / Q000235:genetics; D005473:Fluoxetine / Q000494:pharmacology*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000099153:Pentraxins
D020727:ADP-Ribosylation Factors; D019208:Brain-Derived Neurotrophic Factor; D002097:C-Reactive Protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005473:Fluoxetine; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; D000099153:Pentraxins; C491385:Klf10 protein, rat; C105161:Nrn1 protein, rat; C461219:RNF34 protein, human; C486430:Arl4a protein, rat