Effect of BDNF on aging-related gene expression changes in young and aged rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE14505 | GEO | 2009/01/23
SECONDARY ACCESSION(S): PRJNA114405
REPOSITORIES: GEO
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Project description:Patterns of gene expression in the aged entorhinal cortex and hippocampus were examined one month after entorhinal administration of BDNF lentivirus. Whole-genome patterns of expression were examined using Affymetrix arrays four weeks after entorhinal injection of lentiviral-BDNF or GFP injection compared to control subjects. Experiment Overall Design: 27 Samples total: 4 biological replicates of Age rats BDNF treated, 3 biological replicates of Age rats eGFP treated, and 4 biological replicates each of Aged and Young rats controls for the Entorhinal cortex tissue. 2 biological replicates of Age rats BDNF treated, 2 biological replicates of Age rats eGFP treated, and 4 biological replicates each of Age and Young rats controls for the hippocampus tissue.
2009-01-31 | E-GEOD-14505 | biostudies-arrayexpress
Project description:We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/ß-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. Keywords: Treatment effect
2009-01-23 | GSE14499 | GEO
Project description:We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/Ã-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. Experiment Overall Design: 26 Samples total: 4 biological replicates of APP transgenic mice BDNF treated, 4 biological replicates of APP transgenic mice GFP treated, 3 biological replicates of non-trangenic mice sham lesion and 2 biological replicates of non-transgenic mice GFP treated for both tissues: Entorhinal cortex and hippocampus.
2009-02-01 | E-GEOD-14499 | biostudies-arrayexpress
Project description:Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. Molecular mechanisms of BDNF promoting cellular survival and synaptic plasticity have been intensely studied, yet its role in genome regulation is obscure. Using human induced pluripotent stem cell (hiPSC)-derived neurons via lentiviral delivery of the neuronal transcription factor Ngn2, we performed a temporal profiling (1h, 6h and 10h) of chromatin accessibility upon BDNF treatment or depolarization (KCl) to identify BDNF-specific chromatin-to-gene expression programs.
| EGAS00001006394 | EGA
Project description:Brain-derived Neurotrophic Factor (BDNF) promotes neuronal differentiation and survival and is implicated in the pathogenesis of many neurological disorders. Here, we identified a novel intergenic enhancer located 170 kb from the Bdnf gene, which promotes the expression of Bdnf transcript variants during mouse neuronal differentiation and activity. Following Bdnf activation, enhancer-promoter contacts increase, and the region moves away from the repressive nuclear periphery. Bdnf enhancer activity is necessary for neuronal clustering and dendritogenesis in vitro, and for cortical development in vivo. Our findings provide the first evidence of a regulatory mechanism whereby the activation of a distal enhancer promotes Bdnf expression during brain development.
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Project description:Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory and tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions selectively eliminate senescent cells. In this study, a drug library screen uncovered TrkB (NTRK2) inhibitors as selectively capable of triggering apoptosis of senescent, but not proliferating, human fibroblasts. Senescent cells expressed high levels of TrkB, which supported senescent cell viability, and secreted the TrkB ligand BDNF. The reduced viability of senescent cells after ablating BDNF function supported an autocrine function for TrkB and BDNF, and the increased expression of BCL2L2 through ERK5, downstream of BDNF-TrkB, favored senescent cell survival. Strikingly, treatment with TrkB inhibitors reduced the accumulation of senescent cells in aged mouse organs. Our results suggest that the SASP factor BDNF promotes cell survival by activating TrkB and is a promising therapeutic target to reduce the senescent cell burden.
2022-09-20 | GSE190998 | GEO
Project description:Regenerating new alveolar epithelium is essential for recovery from many lung diseases. This multi-cellular regenerative process occurs when type II alveolar pneumocytes (AT2), with support from mesenchymal niche cells, proliferate to generate more AT2 cells and transdifferentiate in type I pneumocytes. To elucidate how coordinated events between AT2 cells and mesenchyme restore alveolar epithelium we used unbiased genome-wide analysis of chromatin accessibility and gene expression in both cell types following acute lung injury. We observed that chromatin acessability in AT2 cells changes signficantly following acute lung injury. Newly accessible chromatin reveals new STAT3 binding motifs adjacent to genes that regulate essential regenerative pathways in AT2 cells. Restoration of alveolar structures following both sterile and infectious lung injuries was inhibited when STAT3 signaling was lost in AT2 cells. Single-cell transcriptome analysis of regenerating AT2 cells identified brain neurotrophic factor (Bdnf) as the sole STAT3 target gene whose chromatin becomes newly accessible in a regenerating population of AT2 cells. BDNF increased alveolar organoid size and forming efficiency in murine and human models. The receptor for BDNF, TrkB, is uniquely? expressed on mesenchymal alveolar niche cells (MANC). Exposure of BDNF to TrkB increases expression of fibroblast growth factor 7 (Fgf7), an essential regenerative cytokine, in MANCs. Blocking Bdnf signaling with a TrkB receptor antagonist abrogated murine and human alveolar organoid formation. Finally, a small molecule TrkB agonist improved functional and histological outcomes in vivo following sterile and infectious lung injuries. Collectively, these data highlight the biological and therapeutic importance of the Stat3-Bdnf-TrkB axis in orchestrating alveolar epithelial regeneration
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Project description:Regenerating new alveolar epithelium is essential for recovery from many lung diseases. This multi-cellular regenerative process occurs when type II alveolar pneumocytes (AT2), with support from mesenchymal niche cells, proliferate to generate more AT2 cells and transdifferentiate in type I pneumocytes. To elucidate how coordinated events between AT2 cells and mesenchyme restore alveolar epithelium we used unbiased genome-wide analysis of chromatin accessibility and gene expression in both cell types following acute lung injury. We observed that chromatin acessability in AT2 cells changes signficantly following acute lung injury. Newly accessible chromatin reveals new STAT3 binding motifs adjacent to genes that regulate essential regenerative pathways in AT2 cells. Restoration of alveolar structures following both sterile and infectious lung injuries was inhibited when STAT3 signaling was lost in AT2 cells. Single-cell transcriptome analysis of regenerating AT2 cells identified brain neurotrophic factor (Bdnf) as the sole STAT3 target gene whose chromatin becomes newly accessible in a regenerating population of AT2 cells. BDNF increased alveolar organoid size and forming efficiency in murine and human models. The receptor for BDNF, TrkB, is uniquely? expressed on mesenchymal alveolar niche cells (MANC). Exposure of BDNF to TrkB increases expression of fibroblast growth factor 7 (Fgf7), an essential regenerative cytokine, in MANCs. Blocking Bdnf signaling with a TrkB receptor antagonist abrogated murine and human alveolar organoid formation. Finally, a small molecule TrkB agonist improved functional and histological outcomes in vivo following sterile and infectious lung injuries. Collectively, these data highlight the biological and therapeutic importance of the Stat3-Bdnf-TrkB axis in orchestrating alveolar epithelial regeneration
2020-06-01 | GSE132533 | GEO
Project description:This SuperSeries is composed of the following subset Series:; GSE14499: Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease; GSE14505: Effect of BDNF on aging-related gene expression changes in young and aged rats Experiment Overall Design: Refer to individual Series
2009-02-07 | E-GEOD-14522 | biostudies-arrayexpress
Project description:Neuronal activity induced by Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, differentiation, synaptic plasticity, memory formation, and neurocognitive health. Molecular mechanisms of BDNF promoting cellular survival and synaptic plasticity have been intensely studied, yet its role in genome regulation is obscure. Here, through temporal profiling of chromatin accessibility and transcription in mouse primary cortical neurons upon BDNF treatment or depolarization (KCl), we identified BDNF-specific chromatin-to-gene expression programs. Our analyses revealed that enhancer activation is an early event in the regulatory control of BDNF treated neurons, where bZIP pioneered chromatin opening and co-regulatory transcription factors (Homeobox, EGRs, and CTCF) cooperate to induce fine-grained transcription. Deleting such cis-regulatory sequences decreased the BDNF mediated expression of Arc, a key regulator of synaptic plasticity. Furthermore, BDNF-induced accessible regions are linked to preferential exon usage of neurodevelopmental disorder related genes and heritability of neuronal complex traits. In conclusion, this work provides a comprehensive view of BDNF-mediated genome regulatory features and emphasizes the usage of genomic approaches on dissecting mammalian neuronal activity.
2022-09-01 | GSE166959 | GEO