ArticleBMC neuroscience2009
Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice.
Article in BMC neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 44 citations in OpenAlex.
- Exploring the Therapeutic Potential of Benfotiamine in a Sporadic Alzheimer's-Like Disease Rat Model: Insights into Insulin Signaling and Cognitive function.ACS chemical neuroscience · 2024Article
- Endosomal dysfunction contributes to cerebellar deficits in spinocerebellar ataxia type 6.eLife · 2023Article
- Early Life Stress Alters Expression of Glucocorticoid Stress Response Genes and Trophic Factor Transcripts in the Rodent Basal Ganglia.International journal of molecular sciences · 2022Article
- Visualization of activity-regulated BDNF expression in the living mouse brain using non-invasive near-infrared bioluminescence imaging.Molecular brain · 2020Article
- Feeding and food availability modulate brain-derived neurotrophic factor, an orexigen with metabolic roles in zebrafish.Scientific reports · 2020Article
- Visualizing changes in brain-derived neurotrophic factor (BDNF) expression using bioluminescence imaging in living mice.Scientific reports · 2017Article
- New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases.World journal of biological chemistry · 2014Review
- Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice variant translation using a novel drug screening assay: a "quantitative code".The Journal of biological chemistry · 2014Article
- BAC-based cellular model for screening regulators of BDNF gene transcription.BMC neuroscience · 2014Article
- BDNF mediates adaptive brain and body responses to energetic challenges.Trends in endocrinology and metabolism: TEM · 2014Review
- A polymorphism associated with depressive disorders differentially regulates brain derived neurotrophic factor promoter IV activity.Biological psychiatry · 2012Article
- Multiple approaches to investigate the transport and activity-dependent release of BDNF and their application in neurogenetic disorders.Neural plasticity · 2012Review
- Growth arrest and DNA-damage-inducible, beta (GADD45b)-mediated DNA demethylation in major psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
- Identification of cis-elements and transcription factors regulating neuronal activity-dependent transcription of human BDNF gene.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- BAC transgenic mice reveal distal cis-regulatory elements governing BDNF gene expression.Genesis (New York, N.Y. : 2000) · 2010Article
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7 authors at 1 institution in 1 country.
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Abstract
backgroundBrain-derived neurotrophic factor (BDNF) is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC) transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression.
resultsIn this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP). The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA.
conclusionGenomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity.
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