The dentate gyrus (DG) of the hippocampus is one of major targets for antidepressant treatments. Using electroconvulsive stimulation (ECS), a model of highly effective and fast-acting antidepressant therapy, here we show that neural stimulation via ECS induces rapid and lasting dematuration of granule neurons in DG. A single time of stimulation transiently reduced mature marker expression and mature synaptic functions. Repetitive stimulation converted this transient dematuration into a stable form lasting more than 1 month. We compared the activity-dependent neuronal responsiveness in the DG between a single ECS and repeated ECS.
Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment.
Specimen part, Disease, Treatment
View SamplesThe dentate gyrus (DG) of the hippocampus is one of major targets for antidepressant treatments. Our recent research has revealed that selective serotonin reuptake inhibitor (SSRI) treatment causes a long-lasting change in the phenotypes of mature dentate granule neurons to immature state in adult mouse DG. However, it is unknown whether this dematuration of DG is a common effect of antidepressant treatments and what mechanisms underlie it. Using electroconvulsive stimulation (ECS), a model of highly effective and fast-acting antidepressant therapy, here we show that neural stimulation via ECS induces rapid and lasting dematuration of granule neurons in DG. A single or few times of stimulation transiently reduced mature marker expression and mature synaptic functions. Repetitive stimulation converted this transient dematuration into a stable form lasting more than 1 month. Dematured granule neurons showed higher excitability, and an increase in GABA-mediated inhibition by the benzodiazepine diazepam prevented the lasting maintenance phase of dematuration without affecting the initial induction phase. Our study suggests that dematuration of DG is a common cellular mechanism underlying effects of different types of antidepressant treatments, and demonstrate a novel role for excitation/inhibition balance in bidirectional regulation of the state of neuronal maturation in the adult brain.
Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment.
Specimen part
View SamplesRationale Electroconvulsive seizure (ECS) therapy is a nonchemical treatment for depression. Since ECS up-regulates expression of c-Fos in the paraventricular nucleus of hypothalamus (PVN), the function of which is frequently influenced in depression, we hypothesized that ECS modulates functions of the PVN and contributes to its antidepressant effects. Objectives To identify gene expression changes in the mouse PVN by ECS treatment Material and methods First, we established a method to amplify nucleotides from small quantities of RNA. Mice received one shock of ECS and their brains were collected at 2 or 6 h after shock. The PVN was microdissected from dehydrated brain sections, its total RNA was extracted and microarray analysis was applied. Results At 2 h after ECS, 2.6% (589 genes) of the probes showed more than 2-fold decrease, and 0.9% (205 genes) showed more than 2-fold increase. To confirm the expression changes, genes showing differential expression with a wide range in the microarray were analyzed by qPCR. Among the genes with more than 2-fold change by ECS, down-regulated 94 genes and up-regulated 24 genes have been reported the association with anxiety, bipolar disorder or mood disorder by the Ingenuity knowledge database. The groups of down-regulated genes, which are suggested to modulate the function of the PVN or associate to psychiatric disorders, include neuropeptides (Cck), kinases (Prkcb, Prkcc, Camk2a), transcription factors (Bcl6, Tbr1), transporters (Aqp4) and others (Fmr1). Conclusion The present results indicate that ECS treatment can modulate the functions of PVN via a series of gene expression changes, and may contribute to its antidepressant effects at least in part.
Electroconvulsive seizure-induced changes in gene expression in the mouse hypothalamic paraventricular nucleus.
Specimen part, Treatment, Time
View SamplesTo understand the role of prostaglandin (PG) receptor EP2 (Ptger2) signaling in ovulation and fertilization, we investigated time-dependent expression profiles in wild-type (WT) and Ptger2-/- cumuli before and after ovulation by using microarrays.
Expression profiling of cumulus cells reveals functional changes during ovulation and central roles of prostaglandin EP2 receptor in cAMP signaling.
Sex, Specimen part
View SamplesHeart failure (HF) is the most common cause of morbidity and mortality in the developed countries, especially considering the present demographic tendencies in those populations.
Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure.
Specimen part
View SamplesWe purified Atoh1-GFP positive hair cells from organotypic cultures of P1 cochlea 3 hours after 0.5mM gentamicin treatment and performed RNA sequencing to profile the early transcriptional response of hair cells to aminoglycoside antibiotics. Overall design: Levels of mRNA in gentamicin-treated hair cells (three replicates) were compared to untreated hair cells (three replicates). GFP negative, non-hair cells populations from treated organs were compared to those from untreated organs (three replicates for each condition).
Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis in sensory hair cells in the mouse inner ear.
No sample metadata fields
View SamplesWe used single cell RNA-seq to probe the transcriptional responses of utricle supporting cells to damage and Atoh1 transduction. Overall design: mRNA profiles of 4-6 weeks old mice utricle supporting cell cultured for 10 days and supporting cells with overexpression of Atoh1 cultured for 10 days were generated by deep sequencing, using Illumina Nextseq 500.
Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1.
Specimen part, Cell line, Subject
View SamplesWe used RNA-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. Overall design: mRNA profiles of 4-6 weeks old mice utricle endogenous hair cell, supporting cells, supporting cell cultured for 10 days and supporting cells with overexpression of Atoh1 cultured for 10 days were generated by deep sequencing, in duplicate or triplicate, using Illumina Nextseq500 instrument
Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1.
Cell line, Subject
View SamplesAberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and non-cell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1
Constitutively active Akt induces ectodermal defects and impaired bone morphogenetic protein signaling.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View Samples