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Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression.

ABSTRACT: BACKGROUND: Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF) gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of the promoter structure and the mechanisms that mediate developmental and cell-specific expression are still incompletely understood. RESULTS: Comparison of pufferfish and zebrafish BDNF gene sequences as well as 5' RACE revealed three additional 5' exons and associated promoters. RT-PCR with exon-specific primers showed differential developmental and organ-specific expression. Two exons were detected in the embryo before transcription starts. Of the adult organs examined, the heart expressed a single 5' exon whereas the brain, liver and eyes expressed four of the seven 5' exons. Three of the seven 5' exons were not detectable by RT-PCR. Injection of promoter/GFP constructs into embryos revealed distinct expression patterns. The 3' flank profoundly affected expression in a position-dependent manner and a highly conserved sequence (HCS1) present in 5' exon 1c in a dehancer-like manner. CONCLUSIONS: The zebrafish BDNF gene is as complex in its promoter structure and patterns of differential promoter expression as is its murine counterpart. The expression of two of the promoters appears to be regulated in a temporally and/or spatially highly circumscribed fashion. The 3' flank has a position-dependent effect on expression, either by affecting transcription termination or post-transcriptional steps. HCS1, a highly conserved sequence in 5' exon 1c, restricts expression to primary sensory neurons. The tools are now available for detailed genetic and molecular analyses of zebrafish BDNF gene expression.

SUBMITTER: Heinrich G

PROVIDER: S-EPMC442124 | biostudies-literature | 2004 May

REPOSITORIES: biostudies-literature

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Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression.

Heinrich Gerhard G Pagtakhan Carl John CJ

BMC neuroscience 20040521

<h4>Background</h4>Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF) gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of the promoter structure and the mechanisms that mediate developmental and cell-specific expression are still incompletely understood.<h4>Results</h4>Comparison of pufferfish ...[more]

PMID: 15153250

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Project description:BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

Project description:BackgroundPeriodontitis is a common human disease with an increasing incidence. Brain-derived neurotrophic factor (BDNF) is known to play a crucial role in the regeneration of periodontal tissue; however, the expression, methylation level, molecular function, and clinical value of BDNF in periodontitis require further investigation. This study aimed to investigate the expression and potential functions of BDNF in periodontitis.MethodsRNA expression and methylation data were obtained from the Gene Expression Omnibus (GEO) database, and the expression and methylation levels of BDNF were compared between periodontitis and normal tissues. In addition, bioinformatics analysis was performed to investigate the downstream molecular functions of BDNF. Finally, Reverse transcription Quantitative real-time polymerase chain reaction was performed to determine the level of BDNF expression in periodontitis and normal tissues.ResultsGEO database analysis revealed that BDNF was hypermethylated in periodontitis tissues and that its expression was downregulated. Reverse transcription Quantitative real-time polymerase chain reaction confirmed that BDNF expression was downregulated in periodontitis tissues. Several genes that interact with BDNF were determined using a protein-protein interaction network. Functional analysis of BDNF revealed that it was enriched in the Gene Ontology terms cytoplasmic dynein complex, glutathione transferase activity, and glycoside metabolic process. Kyoto Encyclopedia of Genes and Genomes analysis suggested that BDNF was associated with the mechanistic target of rapamycin signaling pathway, fatty acid metabolism, the Janus kinase-signal transducer and activator of transcription signaling pathway, glutathione metabolism, and others. Furthermore, the level of BDNF expression was correlated with the immune infiltration degree of B cells and CD4+ T cells.ConclusionsThis study shown that BDNF was hypermethylated and downregulated in periodontitis tissues, which could be a biomarker and treatment target of periodontitis.

Project description:The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Dataset Information

Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression.

Publications

Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression.

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