Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in adult rat dentate gyrus in vivo.
Brain-derived neurotrophic factor (BDNF) is a critical regulator of transcription-dependent adaptive neuronal responses, such as long-term potentiation (LTP). Brief infusion of BDNF into the dentate gyrus of adult anesthetized rats triggers stable LTP at medial perforant path-granule synapses that is transcription-dependent and requires induction of the immediate early gene Arc. Rather than acting alone, Arc is likely to be part of a larger BDNF-induced transcriptional program. Here, we used cDNA microarray expression profiling to search for genes co-upregulated with Arc 3 h after BDNF-LTP induction. Of nine cDNAs encoding for known genes and up-regulated more than four-fold, we selected five genes, Narp, neuritin, ADP-ribosylation factor-like protein-4 (ARL4L), TGF-beta-induced immediate early gene-1 (TIEG1) and CARP, for further validation. Real-time PCR confirmed robust up-regulation of these genes in an independent set of BDNF-LTP experiments, whereas infusion of the control protein cytochrome C had no effect. In situ hybridization histochemistry further revealed up-regulation of all five genes in somata of post-synaptic granule cells following both BDNF-LTP and high-frequency stimulation-induced LTP. While Arc synthesis is critical for local actin polymerization and stable LTP formation, several of the co-upregulated genes have known functions in excitatory synaptogenesis, axon guidance and glutamate receptor clustering. These results provide novel insight into gene expression responses underlying BDNF-induced synaptic consolidation in the adult brain in vivo.
Wibrand
Karin
K
Department of Biomedicine and Bergen Mental Health Research Center, Section for Physiology, University of Bergen, Jonas Liens vei 91, N-5009 Bergen, Norway.
Messaoudi
Elhoucine
E
Håvik
Bjarte
B
Steenslid
Vibeke
V
Løvlie
Roger
R
Steen
Vidar M
VM
Bramham
Clive R
CR
D000818:Animals; D001369:Axons / Q000502:physiology; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D016172:DNA Fingerprinting; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D017403:In Situ Hybridization; D007267:Injections; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011061:Poly A / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C092069:activity regulated cytoskeletal-associated protein; D011061:Poly A