BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent

Xiang-Ming Zha; John F Bishop; Marlan R Hansen; Luis Victoria; Paul J Abbas; M.Maral Mouradian; Steven H Green

doi:10.1016/S0378-5955(01)00267-2

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BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent

Journal article

Peer reviewed

BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent

Xiang-Ming Zha, John F Bishop, Marlan R Hansen, Luis Victoria, Paul J Abbas, M.Maral Mouradian and Steven H Green

Hearing research, Vol.156(1), pp.53-68

2001

DOI: 10.1016/S0378-5955(01)00267-2

PMID: 11377882

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Abstract

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 Ca 2+/calmodulin-dependent kinases (CaMKs) and the transcription factor, Ca 2+/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.

Spiral ganglion neuron

Brain-derived neurotrophic factor

Cell survival

Ca 2+/calmodulin-dependent protein kinase

Gene expression regulation

Ca 2+/cyclic AMP response element binding protein

Promoter region

Autocrine mechanism

Details

Title: Subtitle: BDNF synthesis in spiral ganglion neurons is constitutive and CREB-dependent
Creators: Xiang-Ming Zha - Departments of Biological Sciences and Otolaryngology, University of Iowa, 138 Biology Building, Iowa City, IA 52242-1324, USA
John F Bishop - Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
Marlan R Hansen - Departments of Biological Sciences and Otolaryngology, University of Iowa, 138 Biology Building, Iowa City, IA 52242-1324, USA
Luis Victoria - Departments of Biological Sciences and Otolaryngology, University of Iowa, 138 Biology Building, Iowa City, IA 52242-1324, USA
Paul J Abbas - Departments of Speech, Pathology and Otolaryngology, University of Iowa, 138 Biology Building, Iowa City, IA 52242, USA
M.Maral Mouradian - Genetic Pharmacology Unit, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
Steven H Green - Departments of Biological Sciences and Otolaryngology, University of Iowa, 138 Biology Building, Iowa City, IA 52242-1324, USA
Resource Type: Journal article
Publication Details: Hearing research, Vol.156(1), pp.53-68
DOI: 10.1016/S0378-5955(01)00267-2
PMID: 11377882
NLM abbreviation: Hear Res
ISSN: 0378-5955
eISSN: 1878-5891
Publisher: Elsevier B.V
Language: English
Date published: 2001
Academic Unit: Communication Sciences and Disorders; Molecular Physiology and Biophysics; Biology; Neurosurgery; Otolaryngology
Record Identifier: 9984006425502771

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