Gabazine treatment of hippocampal organotypic cultures
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE46864 | GEO | 2013/05/14
SECONDARY ACCESSION(S): PRJNA202871
REPOSITORIES: GEO
Similar Datasets
Project description:The blockage of GABA-A ionotropic channels by means of gabazine is a widespread model of plasticity where the increased synaptic activity triggered by Gabazine leads to the up-regulation of a plethora of activity-dependent genes. Here, we sought to characterize the overall transcriptional response of GABA-A blocking of rat hippocampal organotypic cultures. In each of the three biological replica, half of the organotypic hippocampal cultures derived from two rat littermates were treated with gabazine and compared to the untreated ones in order to determine the set of differentially expressed genes.
2013-05-14 | E-GEOD-46864 | biostudies-arrayexpress
Project description:Microarray study of gene expression and molecular interaction pathways in an in vitro model of graded diffuse axonal injury. <br>Mild (10%) and severe (50%) stretch injuries were delivered to rats organotypic hippocampal cultures and mRNA levels were analyzed at 24h. Despite the lack of significant cell death, there was more activation of complex cellular mechanisms following 10% stretch than 50%. IL-1? played a central role in molecular interactions of both injury groups but additional pathways of neurodegeneration involving RhoA were found in 50% stretch.<br><br>
2009-07-04 | E-MEXP-2235 | biostudies-arrayexpress
Project description:Keratinocyte ethnicity affects transcriptomic response of human organotypic raft cultures
2021-03-01 | GSE163711 | GEO
Project description:zeta-potentials of entities such as cells and synaptosomes have been determined, but zeta of brain tissue has never been measured. Electroosmotic flow, and the resulting transport of neuroactive substances, would result from naturally occurring and experimentally or clinically induced electric fields if zeta is significant. We have developed a simple method for determining zeta in tissue. An electric field applied across a rat organotypic hippocampal slice culture (OHSC) drives fluorescent molecules through the tissue by both electroosmotic flow and electrophoresis. Fluorescence microscopy is used to determine each molecule's velocity. Independently, capillary electrophoresis is used to measure the molecules' electrophoretic mobilities. The experiment yields zeta-potential and average tissue tortuosity. The zeta-potential of OHSCs is -22 +/- 2 mV, and the average tortuosity is 1.83 +/- 0.06. In a refined experiment, zeta-potential is measured in various subregions. The zeta-potentials of the CA1 stratum pyramidale, CA3 stratum pyramidal, and dentate gyrus are -25.1 +/- 1.6 mV, -20.3 +/- 1.7 mV, and -25.4 +/- 1.0 mV, respectively. Simple dimensional arguments show that electroosmotic flow is potentially as important as diffusion in molecular transport.
| S-EPMC2480665 | biostudies-literature
Project description:Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse substances later in life, the main purpose of the present study was to compare necrotic/apoptotic corticosterone action in hippocampal organotypic cultures obtained from control animals with the effect of this steroid in tissue from prenatally stressed rats. Because the adverse effects of glucocorticoid action on nerve cell viability appear to result mainly from an increase in the intensity of the effects of glutamate and changes in growth factor and pro-inflammatory cytokine synthesis, the involvement of these factors in corticosterone action were also determined. In stress-like concentration (1 μM), corticosterone, when added to hippocampal cultures for 1 and 3 days, alone or jointly with glutamate, did not induce necrosis. In contrast, in 3-day cultures, corticosterone (1 μM) increased caspase-3 activity and the mRNA expression of the pro-apoptotic Bax. Moreover, corticosterone's effect on caspase-3 activity was stronger in hippocampal cultures from prenatally stressed compared to control rats. Additionally, 24 h of exposure to corticosterone and glutamate, when applied separately and together, increased Bdnf, Ngf, and Tnf-α expression. In contrast, after 72 h, a strong decrease in the expression of both growth factors was observed, while the expression of TNF-α remained high. The present study showed that in stress-like concentrations, corticosterone exerted pro-apoptotic but not necrotic effects in hippocampal organotypic cultures. Prenatal stress increased the pro-apoptotic effects of corticosterone. Increased synthesis of the pro-inflammatory cytokine TNF-α may be connected with the adverse effects of corticosterone on brain cell viability.
| S-EPMC4947107 | biostudies-literature
Project description:Organotypic slice cultures from prostate cancer patients were generated and treated with or without 17b-estradiol or DHT to study estrogen and androgen signalling pathways.
2020-10-06 | GSE142287 | GEO
Project description:Neurogenesis in the adult hippocampus has become an intensively investigated research topic, as it is essential for proper hippocampal function and considered to bear therapeutic potential for the replacement of pathologically lost neurons. On the other hand, neurogenesis itself is frequently affected by CNS insults. To identify processes leading to the disturbance of neurogenesis, we made use of organotypic hippocampal slice cultures (OHSC), which, for unknown reasons, lose their neurogenic potential during cultivation. In the present study, we show by BrdU/Prox1 double-immunostaining that the generation of new granule cells drops by 90% during the first week of cultivation. Monitoring neurogenesis dynamically in OHSC from POMC-eGFP mice, in which immature granule cells are endogenously labeled, revealed a gradual decay of the eGFP signal, reaching 10% of initial values within 7 days of cultivation. Accordingly, reverse transcription quantitative polymerase chain reaction analysis showed the downregulation of the neurogenesis-related genes doublecortin and Hes5, a crucial target of the stem cell-maintaining Notch signaling pathway. In parallel, we demonstrate a strong and long-lasting activation of astrocytes and microglial cells, both, morphologically and on the level of gene expression. Enhancement of astroglial activation by treating OHSC with ciliary neurotrophic factor accelerated the loss of neurogenesis, whereas treatment with indomethacin or an antagonist of the purinergic P2Y12 receptor exhibited potent protective effects on the neurogenic outcome. Therefore, we conclude that OHSC rapidly lose their neurogenic capacity due to persistent inflammatory processes taking place after the slice preparation. As inflammation is also considered to affect neurogenesis in many CNS pathologies, OHSC appear as a useful tool to study this interplay and its molecular basis. Furthermore, we propose that modification of glial activation might bear the therapeutic potential of enabling neurogenesis under neuropathological conditions.
| S-EPMC4870256 | biostudies-literature
Project description:Oral mucosa of smokers is subject to cigarette smoke (CS)-related cytological, genomic, and transcriptional changes that could potentially lead to the development of mouth diseases. In order to further characterize CS effects, we took advantage of two human organotypic in vitro models of the buccal and gingival epithelia (MatTek(R)) that have been developed from the same donor (healthy, non-smoker) to reflect the in vivo situation. Both gingival and buccal organotypic cultures were exposed to fresh, diluted CS at the air-liquid interface in parallel and 4 times (one conventional reference cigarette 3R4F at a time, 1 h intervals, CS dilution with air: 0.46 L/min or 0.16 L/min resulting in CS concentrations of 19.7% and 40.7% (v/v) respectively. Gene expression was captured at time 0 h following the 4th exposure and after different post-exposure time points (4h, 24h, 48h) to investigate time- and concentration-dependent CS effect on both tissues. Other endpoints (e.g. cytotoxicity, pro-inflammatory marker release, cytochrome P450 (CYP) activity, immunohistology) were also measured for some time points. By using computational approaches and by capturing systems biology endpoints, various perturbations of biological processes (e.g. inflammation, cell proliferation, cellular stress) triggered by repeated exposure to CS were analyzed in both buccal and gingival in vitro models. We describe here for the first time the impact of whole CS exposure on human buccal and gingival organotypic in vitro models using various approaches combining systems biology, biological network models, computational methods and standard endpoints.
2014-08-30 | E-MTAB-2251 | biostudies-arrayexpress
Project description:RNA editing is essential for the formation of functional properties of ionotropic glutamate channels. Previously, we demonstrated the regulation of RNA editing upon manipulation with neural activity in vitro. The hypothalamic suprachiasmatic nuclei (SCN), which serve as a master circadian pacemaker depends on glutamatergic neurotransmission, in particular for signal transmission from the retina, and they exhibit spontaneous 24h rhythmical neural activity. We observed changes in the extent of ionotropic glutamate receptor RNA editing in the SCN during the 24h cycle. Therefore, we aimed to understand the overall role of RNA editing for the mechanism of SCN function and to evaluate the impact of RNA under editing on gene expression.
2023-06-29 | E-MTAB-11408 | biostudies-arrayexpress
Project description:Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h following injury and suggest increased calpain activity and membrane disruption as potential underlying mechanisms.
| S-EPMC5338800 | biostudies-literature