PMID- 11377882
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20190822
IS  - 0378-5955 (Print)
IS  - 0378-5955 (Linking)
VI  - 156
IP  - 1-2
DP  - 2001 Jun
TI  - BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent.
PG  - 53-68
AB  - Brain-derived neurotrophic factor (BDNF), which supports spiral ganglion neuron 
      (SGN) survival in vivo and in vitro, is synthesized by SGNs. The BDNF gene 
      generates multiple different transcripts, each from its own promoter region. 
      Using reverse transcriptase-polymerase chain reaction (RT-PCR), we find that SGNs 
      express only the downstream transcripts III and IV in vivo and in vitro. Using 
      RT-PCR assays of BDNF transcripts and transfection of BDNF promoter-reporter 
      constructs, we tested the hypothesis, originally derived from studies of cortical 
      neurons, that depolarization induces BDNF expression via a signaling pathway that 
      includes Ca2+/calmodulin-dependent kinases (CaMKs) and the transcription factor, 
      Ca2+/cyclic AMP response element binding protein (CREB). In contrast, we found 
      that in SGNs in vivo BDNF expression is constitutive and is not increased by 
      electrical activation. Similarly, BDNF expression in vitro is not increased by 
      stimuli that activate CREB, including depolarization, cAMP, or transfection of 
      activated CaMK mutants. However, transfection of dominant-negative CREB mutants 
      did abrogate gene expression driven by BDNF promoters III and IV, indicating that 
      CREB is necessary for constitutive BDNF expression. Thus, BDNF synthesis within 
      SGNs makes possible an autocrine or paracrine mechanism that can contribute to 
      support SGN survival but SGNs are distinctive in that this mechanism is 
      constitutive and not activity-regulated.
FAU - Zha, X M
AU  - Zha XM
AD  - Department of Biological Sciences, University of Iowa, Iowa City 52242-1324, USA.
FAU - Bishop, J F
AU  - Bishop JF
FAU - Hansen, M R
AU  - Hansen MR
FAU - Victoria, L
AU  - Victoria L
FAU - Abbas, P J
AU  - Abbas PJ
FAU - Mouradian, M M
AU  - Mouradian MM
FAU - Green, S H
AU  - Green SH
LA  - eng
GR  - DC00040/DC/NIDCD NIH HHS/United States
GR  - T32 DC000040/DC/NIDCD NIH HHS/United States
GR  - DK25295/DK/NIDDK NIH HHS/United States
GR  - DC02961/DC/NIDCD NIH HHS/United States
GR  - R01 DC002961/DC/NIDCD 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  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Calcium-Calmodulin-Dependent Protein Kinases/physiology
MH  - Cells, Cultured
MH  - Cyclic AMP/physiology
MH  - Cyclic AMP Response Element-Binding Protein/*physiology
MH  - Electrophysiology
MH  - Neurons/*metabolism/physiology
MH  - Promoter Regions, Genetic/physiology
MH  - Rats
MH  - Spiral Ganglion/cytology/*metabolism/physiology
MH  - Up-Regulation
EDAT- 2001/05/30 10:00
MHDA- 2001/08/31 10:01
CRDT- 2001/05/30 10:00
PHST- 2001/05/30 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/05/30 10:00 [entrez]
AID - S0378595501002672 [pii]
AID - 10.1016/s0378-5955(01)00267-2 [doi]
PST - ppublish
SO  - Hear Res. 2001 Jun;156(1-2):53-68. doi: 10.1016/s0378-5955(01)00267-2.