931a6370-b209-4d93-b670-94904d7c8ace - samples
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PROVIDER: EGAD00001009100 | EGA |
REPOSITORIES: EGA
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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: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
Project description:RNA-seq of total RNA from Rad21lox/lox;NexCre/+ and Rad21+/+;NexCre/+ dissociated cortical neurons at Day In Vitro (DIV10) without stimulation or after treatment with TTX/D-AP5 and 1h or 6h of KCl depolarization.
2022-04-26 | GSE172427 | GEO
Project description:Homeostatic plasticity, a form of synaptic plasticity, maintains the fine balance between overall excitation and inhibition in developing and mature neuronal networks. Although the synaptic mechanisms of homeostatic plasticity are well characterized, the associated transcriptional program remains poorly understood. We show that the Kleefstra syndrome-associated protein, EHMT1, plays a critical and cell-autonomous role in synaptic scaling by responding to attenuated neuronal firing or sensory drive. Chronic activity deprivation increased the amount of neuronal dimethylated H3 at lysine 9 (H3K9me2), the catalytic product of EHMT1 and an epigenetic marker for gene repression. Genetic knockdown and pharmacological blockade of EHMT1 or EHMT2 prevented the increase of H3K9me2 and synaptic scaling up. Furthermore, BDNF repression was preceded by EHMT1/2-mediated H3K9me2 deposition at the Bdnf promoter during synaptic scaling up, both in vivo or in vivo. These findings suggest that changes in chromatin state through H3K9me2 governs a repressive program to achieve synaptic scaling. 12 samples (4 conditions in biological triplicate), 3 wt, 3 wt tetradotoxin treated, 3 k.d., 3 k.d. tetradotoxin treated
2016-06-30 | E-GEOD-68960 | biostudies-arrayexpress
Project description:In Alzheimer’s disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, as well as synaptic transmission and plasticity. In addition to compromising canonical BDNF signalling pathways, TrkB-FL cleavage produces an intracellular fragment (TrkB-ICD), which was shown to accumulate in the nucleus and to display tyrosine kinase activity. To dissect the role of TrkB-ICD overexpression from the loss of endogenous signaling throught TrkB-FL, we used lentiviruses to overexpress the TrkB-ICD sequence in cultured primary cortical neurons and performed morphological, electrophysiological and transcriptomics studies. While TrkB-ICD overexpression did not affect cell survival, it caused a significant decrease in the number of dendritic spines, both compared to untransduced and GFP-transduced neurons. Furthermore, TrkB-ICD overexpressing neurons presented a hyperpolarized resting membrane potential and increased frequency of miniature excitatory postsynaptic currents (mEPSCs). Finally, TrkB-ICD overexpression was associated with the upregulation of genes involved in (i) neuronal survival, growth and differentiation; (ii) neuronal cytoarchitecture and spine morphology; (iii) neurodegenerative processes, including AD; and (iv) synaptic transmission and plasticity. Overall, these results show that TrkB-ICD overexpression causes dendritic spine loss, alters excitatory synaptic transmission and causes transcriptome-wide changes, namely in genes coding for proteins involved in synaptic processes.
2024-07-30 | GSE271487 | GEO
Project description:The ability to form memories is a prerequisite for an organismâs behavioural adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell-types, and three time-points before and after contextual learning. Here we show that histone modifications predominantly change during memory acquisition and correlate surprisingly little with changes in gene expression. While long-lasting changes are almost exclusive to neurons, learning-related histone modification and DNA methylation changes occur also in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provides evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring. We examined chromatin modification changes in two distinct mouse brain regions (CA1 and ACC), two cell-types (neurons, non-neurons), and three time-points before and after contextual learning (naive, 1h, 4w).
2015-11-24 | E-GEOD-74966 | biostudies-arrayexpress
Project description:The ability to form memories is a prerequisite for an organismâs behavioural adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell-types, and three time-points before and after contextual learning. Here we show that histone modifications predominantly change during memory acquisition and correlate surprisingly little with changes in gene expression. While long-lasting changes are almost exclusive to neurons, learning-related histone modification and DNA methylation changes occur also in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provides evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring. We examined chromatin modification changes in two distinct mouse brain regions (CA1 and ACC), two cell-types (neurons, non-neurons), and three time-points before and after contextual learning (naive, 1h, 4w).
2015-11-24 | E-GEOD-74965 | biostudies-arrayexpress
Project description:Foxp2 heterozygous mice and wildtype mice were injected with cocaine or saline, 1h post-injection nucleus acumbens RNA was extracted and analysed We have tested a potential role for the transcription factor Foxp2 in dopamine signaling and reward associated synaptic plasticity and behavior. We found that Foxp2 is acutely downregulated in reward associated circuits in the nucleus accumbens following a single injection of cocaine. In Foxp2 heterozygous mutant mice, loss of transcriptional suppression by Foxp2 causes an increased constitutive expression of dopamine signaling related genes which corresponds with impairments in synaptic plasticity and reward associated behaviors.
2023-08-31 | GSE47457 | GEO
Project description:Homeostatic plasticity, a form of synaptic plasticity, maintains the fine balance between overall excitation and inhibition in developing and mature neuronal networks. Although the synaptic mechanisms of homeostatic plasticity are well characterized, the associated transcriptional program remains poorly understood. We show that the Kleefstra syndrome-associated protein, EHMT1, plays a critical and cell-autonomous role in synaptic scaling by responding to attenuated neuronal firing or sensory drive. Chronic activity deprivation increased the amount of neuronal dimethylated H3 at lysine 9 (H3K9me2), the catalytic product of EHMT1 and an epigenetic marker for gene repression. Genetic knockdown and pharmacological blockade of EHMT1 or EHMT2 prevented the increase of H3K9me2 and synaptic scaling up. Furthermore, BDNF repression was preceded by EHMT1/2-mediated H3K9me2 deposition at the Bdnf promoter during synaptic scaling up, both in vivo or in vivo. These findings suggest that changes in chromatin state through H3K9me2 governs a repressive program to achieve synaptic scaling.
2016-06-30 | GSE68960 | GEO
Project description:The cAMP responsive element binding protein (CREB) pathway has been involved in two major cascades of gene expression regulating neuronal function. The first one presents CREB as a critical component of the molecular switch that control longlasting forms of neuronal plasticity and learning. The second one relates CREB to neuronal survival and protection. To investigate the role of CREB-dependent gene expression in neuronal plasticity and survival in vivo, we generated bitransgenic mice expressing A-CREB, an artificial peptide with strong and broad inhibitory effect on the CREB family, in forebrain neurons in a regulatable manner. The expression of ACREB in hippocampal neurons impaired L-LTP, reduced intrinsic excitability and the susceptibility to induced seizures, and altered both basal and activity-driven gene expression. In the long-term, the chronic inhibition of CREB function caused severe loss of neurons in the CA1 subfield as well as in other brain regions. Our experiments confirmed previous findings in CREB deficient mutants and revealed new aspects of CREB-dependent gene expression in the hippocampus supporting a dual role for CREB-dependent gene expression regulating intrinsic and synaptic plasticity and promoting neuronal survival. manufacturer's protocol. Experiment Overall Design: Each sample contained total RNA from the hippocampi of a group of 3-4 three weeks old mice. We obtained duplicate samples for each experimental condition (in total 14 WT and 20 A-CREB mice where used in this experiment). Mouse Genome 430 2.0 genechips were hybridized, stained, washed and screened for quality according to the manufacturer's protocol.
2009-01-17 | E-GEOD-14320 | biostudies-arrayexpress