PMID- 23436435 OWN - NLM STAT- MEDLINE DCOM- 20130930 LR - 20220309 IS - 1098-1063 (Electronic) IS - 1050-9631 (Linking) VI - 23 IP - 5 DP - 2013 May TI - Regulation of the spatial code for BDNF mRNA isoforms in the rat hippocampus following pilocarpine-treatment: a systematic analysis using laser microdissection and quantitative real-time PCR. PG - 413-23 LID - 10.1002/hipo.22100 [doi] AB - Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity and is one of those genes that generate multiple mRNAs with different alternatively spliced 5'UTRs. The functional significance of many BDNF transcripts, each producing the same protein, is emerging. On the basis of the analysis of the four most abundant brain BDNF transcripts, we recently proposed the "spatial code hypothesis of BDNF splice variants" according to which the BDNF transcripts, through their differential subcellular localization in soma or dendrites, represent a mechanism to synthesize the protein at distinct locations and produce local effects. In this study, using laser microdissection of hippocampal laminae and reverse transcription-quantitative real-time PCR (RT-qPCR), we analyzed all known BDNF mRNA variants at resting conditions or following 3 h pilocarpine-induced status epilepticus. In untreated rats, we found dendritic enrichment of BDNF transcripts encoding exons 6 and 7 in CA1; exons 1, 6, and 9a in CA3; and exons 5, 6, 7, and 8 in DG. Considering the low abundance of the other transcripts, exon 6 was the main transcript in dendrites under resting conditions. Pilocarpine treatment induced an increase of BDNF transcripts encoding exons 4 and 6 in all dendritic laminae and, additionally, of exon 2 in CA1 stratum radiatum and exons 2, 3, 9a in DG molecular layer while the other transcripts were decreased in dendrites, suggesting restriction to the soma. These results support the hypothesis of a spatial code to differentially regulate BDNF in the somatic or dendritic compartment under conditions of pilocarpine-induced status epilepticus and, furthermore, highlight the existence of subfield-specific differences. CI - Copyright (c) 2013 Wiley Periodicals, Inc. FAU - Baj, Gabriele AU - Baj G AD - Department of Life Science, B.R.A.I.N. Center for Neuroscience, University of Trieste, Trieste, Italy. FAU - Del Turco, Domenico AU - Del Turco D FAU - Schlaudraff, Jessica AU - Schlaudraff J FAU - Torelli, Lucio AU - Torelli L FAU - Deller, Thomas AU - Deller T FAU - Tongiorgi, Enrico AU - Tongiorgi E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130225 PL - United States TA - Hippocampus JT - Hippocampus JID - 9108167 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Muscarinic Agonists) RN - 0 (RNA, Messenger) RN - 01MI4Q9DI3 (Pilocarpine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Dendrites/drug effects/metabolism MH - Gene Expression Regulation/*drug effects MH - Hippocampus/cytology/*drug effects/metabolism MH - Male MH - Microdissection MH - Muscarinic Agonists/*pharmacology MH - Neurons/cytology/drug effects MH - Pilocarpine/*pharmacology MH - RNA, Messenger/*metabolism MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Statistics, Nonparametric EDAT- 2013/02/26 06:00 MHDA- 2013/10/01 06:00 CRDT- 2013/02/26 06:00 PHST- 2013/01/08 00:00 [accepted] PHST- 2013/02/26 06:00 [entrez] PHST- 2013/02/26 06:00 [pubmed] PHST- 2013/10/01 06:00 [medline] AID - 10.1002/hipo.22100 [doi] PST - ppublish SO - Hippocampus. 2013 May;23(5):413-23. doi: 10.1002/hipo.22100. Epub 2013 Feb 25.