Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel anti-epileptogenesis strategy of temporal lobe epilepsy based on nitric oxide donor

ABSTRACT: The molecular mechanism underlying the role of hippocampal hilar interneuron degeneration in temporal lobe epilepsy (TLE) remains unclear. Especially, very few studies have focused on the role of neuronal nitric oxide synthase (nNOS, encoded by Nos1) containing hilar interneurons in TLE. In the present study, Nos1 conditional knockout mice were constructed, and we found that selective deletion of Nos1 in hilar interneurons rather than dentate granular cells (DGCs) triggered epileptogenesis. The level of nNOS was downregulated in patients and mice with TLE. Nos1 deletion led to excessive epilepsy-like excitatory input circuit formation and hyperexcitation of DGCs. Replenishment of hilar nNOS protein blocked epileptogenic development and memory impairment in pilocarpine-induced TLE mice. Moreover, chronic treatment with DETA/NONOate, a slowly released exogenous nitric oxide (NO) donor, prevented aberrant neural circuits of DGCs and the consequent epileptogenesis without acute antiseizure effects. Therefore, we concluded that NO donor therapy may be a novel anti-epileptogenesis strategy, different from existing antiseizure medications (ASMs), for curing TLE.

ORGANISM(S): Mus musculus

PROVIDER: GSE274303 | GEO | 2024/10/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide analysis of H3K4me3 in NOS1+ mouse enteric neurons

2024-02-14 | GSE139479 | GEO

Genome-wide analysis of HIF1A and ARNT binding in N1E115 cells

Project description:Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we analyzed HIF1A and ARNT binding by chromatin immunoprecipitation-sequencing.

2024-02-14 | GSE139477 | GEO

Transcriptome analysis of N1E115 cells cultured in the presence of 20% or 4% O2

Project description:Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we performed transcriptome analysis using stranded total RNA-sequencing.

2024-02-14 | GSE139472 | GEO

Chromosome conformation analysis of N1E115 cells by HiC

2024-02-14 | GSE139470 | GEO

Genome-wide analysis of histone marks in N1E115 cells

Project description:Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we analyzed the genome-wide distribution of the histone marks H3K27ac, H3K27me3, H3K36me3, H3K4me1, and H3K4me3 by chromatin immunoprecipitation-sequencing.

2024-02-14 | GSE139478 | GEO

Genome-wide analysis of POLR2, CTCF, RAD21, and H3K9ac binding in N1E115 cells

Project description:Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we analyzed the genome-wide distribution of CTCF, RAD21, total and S2- or S5-phosphorylated RNA polymerase II, and the histone mark H3K9ac by chromatin immunoprecipitation-sequencing.

2024-02-14 | GSE139481 | GEO

iTRAQ-based proteomic analysis of dentate gyrus in temporal lobe epilepsy with hippocampal sclerosis

Project description:Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment and mostly present with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis(HS). However, the underlying molecular mechanisms involved remain poorly characterized. Dentate gyrus(DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) -based quantitative proteomic technique was performed to analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from the autopsy. Our proteomic data identified 5583 proteins, of which 82 proteins were up-regulated and 90 proteins were down-regulated. Bioinformatics analysis indicated that differential expressed proteins enriched in “synaptic vesicle”, “mitochondrion”, “cell-cell adhesion”, “regulation of synaptic plasticity”, “ATP binding” and “Oxidative phosphorylation”. Protein-protein interaction network analysis found a pivotal module of 10 proteins that relate to “Oxidative phosphorylation”. This study is the first to investigate proteomic alterations in DG region of TLE-HS patients, and pave the way to better understanding of epileptogenesis mechanisms and future therapeutic intervention.

2021-01-18 | PXD023048 | Pride

Protein expression in MOCK and neuronal nitric oxide synthase 1 (NOS1) transduced SH-SY5Y human neuroblastoma cells on stimulation with rapamycin or serum free starvation

Project description:Neuronal nitric oxide synthase (nNOS/NOS1) is upregulated in the aging brain and contributes to age-and stress-associated neuronal dysfunctions. To mimic this situation for the study of underlying mechanisms we generated a cell model in which human SH-SH5Y neuroblastoma cells constitutively express NOS1 at a level comparable with the rodent brain, whereas the control cells have only low levels. SH-SY5Y cells are the most widely used cell model for neurodegenerative and aging research. They were stably transduced with a lentiviral vector for NOS1 and FACS sorted. Control cells were transduced with the backbone vector, referred to as MOCK or "WT-LV205". Neuronal aging of SH-SY5Y can be imposed with a number of pharmacological, genetic or stress stimuli including retinoic acid and repeated cycles of starvation. Hence, to further challenge the cells we imposed proteostasis stress by treatment with 1 µM rapamycin for 24h or culture in serum-free medium for 24h. Control cells were cultured in full medium, which was RPMI 1640 medium supplemented with heat-inactivated 10% fetal bovine serum, 100 U/ml penicillin/streptomycin, and 2 mM glutamine. All cells were kept at 37°C in 5% CO2 atmosphere in a humidified tissue culture incubator. Rapamycin elicits mTOR dependent autophagy, whereas starvation is a stimulus for chaperone-mediated autophagy, but also affects proteolysis by the proteasome and lysosome and eventually, ER stress. During stimulation, all cells were supplemented with NOS cofactors including 10 µM NAD, 40 µM NADPH, and 100 µM tetrahydrobiopterin. The proteome data set shows nNOS/NOS1-dependent alterations of protein expression in SH-SY5Y neuroblastoma cells in full medium, on stimulation with rapamycin or exposure to serum-free starvation.

2018-10-17 | PXD010538 | Pride

Mapping Interactions of Calmodulin and nNOS by CXL-MS

Project description:Neuronal nitric oxide synthase (nNOS) is a self-sufficient homodimeric cytochrome P450-like enzyme that catalyzes the conversion of L-arginine to nitric oxide in the presence of NADPH and molecular oxygen. The binding of calmodulin (CaM) to a linker region between the FAD/FMN containing reductase domain and the heme containing oxygenase domain, greatly enhances electron transfer reactions allowing reduction of the heme and NO synthesis. Due to the dynamic nature of the nNOS reductase domain and the overall low resolution of full-length nNOS structures, the exact nature of the CaM-bound active complex during heme reduction is still unresolved. Interestingly, hydrogen-deuterium exchange and mass spectrometry (HDX-MS) studies on iNOS, but not nNOS, directly revealed interactions of the FMN-domain and CaM with the oxygenase domain. To further address this unexpected finding with nNOS, we utilized covalent crosslinking and mass spectrometry (CXL-MS) to examine interactions of CaM with full- length nNOS. Specifically, MS-cleavable bifunctional crosslinker disuccinimidyl dibutyric urea was used to identify thirteen unique crosslinks between CaM and nNOS as well as 61 crosslinks within the nNOS. Detailed analysis of the crosslinks provide evidence for CaM interaction with the oxygenase and reductase domain residues as well as interactions of the FMN-domain with the oxygenase dimer. Crosslink-guided docking studies reveal a conformation of nNOS that brings the FMN within 15 Å to the heme and provides further support for a more compact conformation of CaM-bound nNOS than previously observed in EM-derived structures. These studies also point to the utility of CXL-MS to capture transient dynamic conformations that may not be captured by HDX-MS experiments.

2024-01-26 | PXD044750 | Pride

Bulk RNA-seq data from the dopaminergic neurons, MB output neurons, Kenyon cells, APL and DPM neurrons in adult Drosophila

Project description:We analyzed transcriptome of the mushroom body cell types to identify cotransmitters of dopaminergic neurons. We found that the full-lengh splicing isoform of nitric oxide synthase (NOS1) is enriched in two types of dopaminergic neurons, and validated the results by in-situ hybridization and immunohistochemistry.

2019-11-05 | GSE139889 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data