PMID- 8415610
OWN - NLM
STAT- MEDLINE
DCOM- 19931110
LR  - 20220309
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 90
IP  - 19
DP  - 1993 Oct 1
TI  - Differential usage of multiple brain-derived neurotrophic factor promoters in the 
      rat brain following neuronal activation.
PG  - 8802-6
AB  - The rat brain-derived neurotropic factor (BDNF) gene consists of four 5' exons 
      linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. To 
      gain insights into the regulation of BDNF mRNA expression, probes specific for 
      the different 5' exons were used to study the expression of BDNF mRNA in the 
      brain. Following a systemic injection of the glutamate analog kainic acid, exon 
      I, II, and III mRNAs increased transiently in hippocampus and cerebral cortex. A 
      modest increase was seen for exon IV, where a new transcription initiation site 
      was induced by this treatment. Pretreatments with the N-methyl-D-aspartate (NMDA) 
      receptor antagonist MK801 or the 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor 
      antagonist 2,3-dihydroxy-6-nitrosulfanoylbenzo(f)quinoxaline revealed two 
      region-specific patterns of glutamate receptor-mediated regulation. The first 
      pattern found in neocortex, piriform cortex, and amygdala involves regulation of 
      BDNF exon I, II, and III mRNAs through NMDA and AMPA/kainate receptors. The 
      second pattern found in the hippocampus involves regulation of BDNF exon I, II, 
      and III mRNAs by high-affinity kainate or metabotropic receptors. Treatment with 
      the gamma-aminobutyric acid subtype A (GABAA) receptor antagonist bicuculline 
      increased exon I and III mRNAs in the denate gyrus, and the muscarinic receptor 
      agonist pilocarpine increased exon I mRNA mainly in the neocortex. These data 
      show that the four BDNF promoters allow multiple points of BDNF mRNA regulation 
      and suggest that the activation of different subtypes of glutamate receptors 
      differentially regulates the expression of BDNF exon-specific mRNAs in the brain.
FAU - Metsis, M
AU  - Metsis M
AD  - Department of Medical Chemistry (II), Karolinska Institute, Stockholm, Sweden.
FAU - Timmusk, T
AU  - Timmusk T
FAU - Arenas, E
AU  - Arenas E
FAU - Persson, H
AU  - Persson H
LA  - eng
GR  - AG04418/AG/NIA NIH HHS/United States
GR  - NSO9199/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antisense Elements (Genetics))
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA Probes)
RN  - 0 (RNA, Messenger)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Antisense Elements (Genetics)
MH  - Blotting, Northern
MH  - Brain/metabolism/*physiology
MH  - Brain-Derived Neurotrophic Factor
MH  - Exons
MH  - Gene Expression/drug effects
MH  - In Situ Hybridization
MH  - Kainic Acid/pharmacology
MH  - Male
MH  - Nerve Growth Factors/biosynthesis/genetics
MH  - Nerve Tissue Proteins/*biosynthesis/*genetics
MH  - Neurons/drug effects/metabolism/*physiology
MH  - Organ Specificity
MH  - *Promoter Regions, Genetic
MH  - RNA Probes
MH  - RNA, Messenger/biosynthesis/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC47448
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
PMCR- 1994/04/01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
PHST- 1994/04/01 00:00 [pmc-release]
AID - 10.1073/pnas.90.19.8802 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8802-6. doi: 10.1073/pnas.90.19.8802.