NBQX AMPA receptor antagonist in vitro treatment of human smooth muscle cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB43287 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR5396104.fastq.gz | Fastqsanger.gz | |||
| ERR5396105.fastq.gz | Fastqsanger.gz | |||
| ERR5396106.fastq.gz | Fastqsanger.gz | |||
| ERR5396107.fastq.gz | Fastqsanger.gz | |||
| ERR5396108.fastq.gz | Fastqsanger.gz |
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Project description:Chronic stress is a key risk factor for a variety of diseases, but the determinants of individual stress susceptibility are still unclear. Using a recently developed paradigm for chronic social stress in mice we identified animals that were resistant or susceptible to the persistent effects of chronic stress exposure. Gene expression analysis in laser-microdissected hippocampal subfields of both groups revealed differentially regulated AMPA receptor subunits, which might affect the susceptibility of an individual to chronic social stress. To test this hypothesis, animals were treated with the AMPA receptor potentiator LY451646 or vehicle during the last 4 weeks of chronic stress exposure. Enhanced AMPA receptor function in chronically stressed animals ameliorated the lasting effects of the chronic stress exposure on physiological, neuroendocrine and behavioural parameters. Our data suggest that differences in AMPA receptor function may underlie individual stress susceptibility and support AMPA receptor potentiators as potential medication in stress-related diseases. Keywords: phenotype, chronic stress, AMPA We have subjected 120 individuals to the chronic social stress procedure, which was recently shown to result in robust effects on neuroendocrine and behavioural parameters (Sterlemann V, 2008). Following the stress procedure all animals were single housed for 7 days. Corticosterone secretion was significantly increased in the chronic stress group compared to controls after one week of single housing. Within the chronic stress group we observed a large variation, where some individuals had recovered from the stress procedure, while others still showed a largely increased corticosterone secretion. After 4 more weeks of single housing, the difference in basal corticosterone secretion between the animals susceptible to chronic stress and unsusceptible or control subjects was still evident. From the group extremes in the chronically stressed animals we selected the 6 most-affected and the 6 most resistant individuals. To investigate the mechanisms underlying the observed differences in individual stress susceptibility between these mice we laser dissected the CA1 and the dentate gyrus region of the hippocampus in the selected mice and performed a gene expression profiling analysis. Pooled amplified RNA samples were then hybridised on Illumina mouse BeadChips (N=4 per group) and detected in the Illumina BeadArray Reader (Illumina, Inc., San Diego, CA).
2010-10-25 | E-GEOD-11211 | biostudies-arrayexpress
Project description:AMPA receptors are involved not only in neuronal plasticity but also in excitotoxicity, mediated largely by the influx of Ca2+ (Choi et al., 1988). Their implication has been highlighted in animal models of ischemia and epilepsy. Studies of ischemic rodent models featured that prior to cell death, hippocampal CA1 pyramidal cells exhibit an increased AMPA receptor-mediated Ca2+ influx and decreased GluR2 and GluR3 mRNA and protein levels (Gorter et al., 1997; Heuerteaux et al., 1995). A total of 15 RNA samples were analyzed. Cultured murine primary cortical neurons were treated with 300uM AMPA over a time-course of 5h, 15h and 24h (n=3) in addition to the vehicle control (n=6).
2013-12-31 | E-GEOD-22993 | biostudies-arrayexpress
Project description:Chronic stress is a key risk factor for a variety of diseases, but the determinants of individual stress susceptibility are still unclear. Using a recently developed paradigm for chronic social stress in mice we identified animals that were resistant or susceptible to the persistent effects of chronic stress exposure. Gene expression analysis in laser-microdissected hippocampal subfields of both groups revealed differentially regulated AMPA receptor subunits, which might affect the susceptibility of an individual to chronic social stress. To test this hypothesis, animals were treated with the AMPA receptor potentiator LY451646 or vehicle during the last 4 weeks of chronic stress exposure. Enhanced AMPA receptor function in chronically stressed animals ameliorated the lasting effects of the chronic stress exposure on physiological, neuroendocrine and behavioural parameters. Our data suggest that differences in AMPA receptor function may underlie individual stress susceptibility and support AMPA receptor potentiators as potential medication in stress-related diseases. Keywords: phenotype, chronic stress, AMPA
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Project description:Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming axo-somatic synapses with inner hair cells (IHCs), the primary sensory receptors of the mammalian cochlea. Although IHC ribbon synapses have been extensively studied, the molecular mechanisms regulating the structure and function of the post-synaptic density (PSD) at the SGN afferent terminals are largely unknown. Using functional, morphological, and transcriptomic approaches, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1), encoded by the Adgrb1 gene, is required for the clustering of the glutamate AMPA receptors GluR2-4 to the SGN post-synaptic density. Adult mice expressing BAI1 lacking the N-terminal thrombospondin type 1 repeats (TRS) have functional IHC synapses but fail to transmit acoustic information to the SGNs, leading to highly raised auditory thresholds. We also found that in adult Bai1-deficient mice, despite the almost complete absence of AMPA receptors, the SGN fibres innervating the IHCs did not degenerate. RNA sequencing and western blotting also indicate that AMPA receptors are expressed in the cochlea of Bai1-deficient mice, highlights that BAI1 is involved is trafficking or anchoring GluR2-4 to the PSDs. Moreover, these results have identified novel molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.
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Project description:AMPA receptors are involved not only in neuronal plasticity but also in excitotoxicity, mediated largely by the influx of Ca2+ (Choi et al., 1988). Their implication has been highlighted in animal models of ischemia and epilepsy. Studies of ischemic rodent models featured that prior to cell death, hippocampal CA1 pyramidal cells exhibit an increased AMPA receptor-mediated Ca2+ influx and decreased GluR2 and GluR3 mRNA and protein levels (Gorter et al., 1997; Heuerteaux et al., 1995).
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Project description:The aim of the study was to characterize the molecular mechanism involved in TGF-M-CM-^_ mediated smooth muscle formation in vitro. We employed rat bone marrow derived Oct4 expressing clones of multipotent adult progenitor cells (rMAPC). We subjected these cells to differentiation towards smooth muscle cell as previously reported using TGF-M-CM-^_1. The differentiation process reuires 6 days with media change every 2 days followed by RNA harvest. RNA was isolated using commercially available kits (Qiagen RNA easy micro kit). RNA integrity and quality was assessed prior to labeling and hybridization. As a control RNA from rat aortic smooth muscle cells was commercially obtained. Two biological replicate clones of rMAPC cells were used for the differentiation to smooth muscle like cells. The RNA was harvested at days 0, 2, 4 and 6 in triplicates. The RNA from primary smooth muscle cells was commercially obtained and was used in duplicates as control.
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