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: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: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
Project description:Chromatin methylation has emerged as a critical modulator of neuronal plasticity and cognitive function. Notwithstanding, the role of enzymes that demethylate DNA remain to be fully explored. Here we report that loss of ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), in adult neurons enhances cognitive function. In the adult mouse hippocampus, we detected an enrichment of Tet2 in neurons. Abrogation of neuronal Tet2 in vitro altered synaptic-plasticity related gene expression. We observed that loss of Tet2 in mature glutamatergic neurons in adult mice resulted in differential hydroxymethylation on genes involved in synaptic transmission in the hippocampus. Correspondingly, RNA sequencing identified changes in both long-term potentiation pathways and immune-related genes linked to synaptic plasticity. Functionally, loss of neuronal Tet2 improved performance on hippocampal-dependent spatial and associative memory tasks. Ultimately, this work identifies neuronal Tet2 as a molecular target to enhance cognitive function.
2021-04-13 | GSE171947 | GEO
Project description:Remote memory and cortical synaptic plasticity require neuronal CCCTC-binding factor (CTCF), a central organizer of 3D chromatin architecture
| PRJNA387605 | ENA
Project description:Impairment of synaptic plasticity is involved in a range of pathological conditions such as cognitive deficits. However, how synaptic efficacy is regulated is not fully understood. Here, we report that the epigenetic factor Jade family PHD finger 2 (JADE2), which is upregulated by neuronal activities, is critically involved in the maintenance of hippocampal synaptic plasticity and cognitive functions in mice. Knockdown or genetic deletion of JADE2 in hippocampal CA1 results in impaired structural and functional synaptic plasticity, leading to memory impairment, whereas overexpression of JADE2 in CA1 neurons facilitates hippocampal-dependent learning and memory. Mechanistically, we show that JADE2 modulates synaptic functions mainly by transcriptional activation of cytoskeletal protein RAC1, and this activity is dependent on its interaction with histone acetyltransferase HBO1. Together, our findings suggest JADE2 is a critical player for experience-dependent gene regulation in controlling synaptic plasticity and cognitive functions.
2022-04-11 | GSE197460 | GEO
Project description:Primary cultures of Cerebellar Granule Neurons (CGNs) have been extensively utilized to examine the signal transduction mechanisms underlying neuronal apoptosis. We conducted whole-genome expression profiling to decipher the transcriptional program controlling the apoptotic/survival switch in cerebellar granule neurons (CGNs) following the induction of apoptosis by serum and potassium deprivation and their rescue by gastric inhibitory polypeptide (Gip), substance p (Sp), insulin-like growth factor-1 (Igf1) or pituitary adenylyl cyclase-activating polypeptide (Pacap). Our results reveal the transcriptional changes intersecting neuronal apoptosis and survival and form the basis for further functional analyses and pharmacological exploitation to identify neuroprotective drugs. After six days âin vitroâ (DIV), extracellular KCl of CGNs was shifted from 25 to 5 mM for neuronal apoptotic death induction. After two washes with serum-free BME containing 5 mM KCl, neurons were incubated with the same medium for 6 h (K5), while control neurons were incubated with serum free medium supplemented with 25 mM KCl (K25). K5 neurons were also treated with a maximal effective dose of Gip, Sp, Igf1 and Pacap. Four biological replicates (derived from the same litter) for each of the experimental conditions (K25, K5, K5 + Gip; K25, K5, K5 + Sp; K25, K5, K5 + Igf1; K25, K5, K5 + Pacap) were analyzed.
2016-07-03 | E-GEOD-67788 | biostudies-arrayexpress
Project description:We performed RNA-seq of E16.5 mouse cortical neurons depolarized with 55mM KCl for 0h, 2h and 6h.
2022-11-02 | GSE201636 | GEO