Rattus norvegicus
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PROVIDER: PRJNA234394 | ENA |
REPOSITORIES: ENA
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Project description:The present study has used whole-rat genome microarray expression profiling to identify genes whose expression is significantly altered in hippocampal neuronal cultures submitted to oxygen and glucose deprivation (OGD), an established in vitro model for cerebral global ischemia that is suitable for investigations at the molecular level. To do so, total RNA was extracted from hippocampal neuronal cultures at an early (7h) and delayed (24h) time point after OGD, as well as from control neurons. Analysis of gene ontology showed that OGD followed by 7h or 24h of recovery induces changes in the expression levels of genes related with inflammation, response to oxidative stress, metabolism, apoptosis, synaptic proteins and ion channels and, importantly, genes that show different expression levels are mainly specific to one of the two time points of recovery analyzed. The expression levels of several genes were confirmed by qPCR and were in good agreement with the microarray data, showing that the combined use of the OGD model and the microarray technology can be a useful tool for the study molecular mechanisms contributing to the neuronal demise after transient global ischemia. Ischemia induced gene expression in primary hippocampal neuronal rat cultures was measured at 7 and 24 hours after exposure to Oxygen and Glucose deprivation (OGD). Three independent experiments were performed at each time (7 or 24 hours) as independent biological replicates.
2014-06-16 | E-GEOD-54037 | biostudies-arrayexpress
Project description:Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.
2020-12-14 | GSE161540 | GEO
Project description:<p><em>Gastrodia elata</em> Blume (GE) has been widely used to treat various central and peripheral nerve diseases, and P-Hydroxybenzaldehyde (PHBA) is one of the indicative components of GE brain protection. Since the previous study of our group found that PHBA has a good effect on protecting mitochondria against cerebral ischemia-reperfusion injury in rats (I/R). We will further explore how PHBA regulates the metabolic mechanism in blood after cerebral I/R to find an effective therapeutic target to prevent and treat IS. Firstly, using the rat model of cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion/Reperfusion (MCAO/R). The therapeutic effect of PHBA on brain I/R was evaluated by neurological function score, triphenyl tetrazolium chloride (TTC), Hematoxylin and eosin (HE), and Nissl staining. Secondly, a non-targeted metabonomic based on HPLC-QTOF-MS/MS was established to identify differential metabolites. Finally, we analyzed a targeted metabolic spectrum and verified the potential therapeutic targets. The results showed that the neurological function score, cerebral infarction area, hippocampal morphology, and the number of neurons in the PHBA group were significantly improved compared with the model group. Metabonomic analysis showed that 13 different metabolites were identified between the model and PHBA group, which may be involved in the 'tricarboxylic acid cycle', 'glutathione metabolism', 'mutual transformation of pentose and glucuronates', and so on. Among them, the most significant differential metabolite, dGMP, decreased significantly after PHBA treatment. We used WB to verify the expression of membrane-associated guanosine kinase PSD-95 and The subunit of glutamate AMPA receptor GluA1, which significantly increased after PHBA treatment. In addition, we also found that PHBA increased the expression of the light chain-3 protein (LC3) and autophagy effector protein 1 (Beline1) in WB while decreasing the expression of sequestosome-1 (p62), indicating that autophagy activity was promoted. Similarly, in TUNEL staining and detection of apoptosis-related proteins, it was found that MCAO/R up-regulated the expression of Bax and Cleaved-caspase-3 while down-regulated the expression of Bcl-2, and increased the apoptosis of hippocampal neurons, but PHBA could improve this situation. In summary, these results suggest that cerebral I/R causes postsynaptic dysfunction by disrupting the interaction between PSD-95 and AMPARs, and the inhibition of the autophagy system eventually leads to the apoptosis of hippocampal neurons.</p>
2024-07-04 | MTBLS7870 | MetaboLights
Project description:Counter to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The causal role of active DNA demethylation in neurons, however, is not known. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair pathway. Here, we show that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of base-excision repair in hippocampal neurons elevates excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreases it. Furthermore, dysregulation of Tet3 signalling prevents homeostatic synaptic plasticity. Mechanistically, Tet3 dictates neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate basic properties and meta-plasticity of neurons via active DNA demethylation.
2015-03-25 | GSE67245 | GEO
Project description:The present study has used whole-rat genome microarray expression profiling to identify genes whose expression is significantly altered in hippocampal neuronal cultures submitted to oxygen and glucose deprivation (OGD), an established in vitro model for cerebral global ischemia that is suitable for investigations at the molecular level. To do so, total RNA was extracted from hippocampal neuronal cultures at an early (7h) and delayed (24h) time point after OGD, as well as from control neurons. Analysis of gene ontology showed that OGD followed by 7h or 24h of recovery induces changes in the expression levels of genes related with inflammation, response to oxidative stress, metabolism, apoptosis, synaptic proteins and ion channels and, importantly, genes that show different expression levels are mainly specific to one of the two time points of recovery analyzed. The expression levels of several genes were confirmed by qPCR and were in good agreement with the microarray data, showing that the combined use of the OGD model and the microarray technology can be a useful tool for the study molecular mechanisms contributing to the neuronal demise after transient global ischemia.
2014-06-16 | GSE54037 | GEO
Project description:Gene expression profiles of Ngn3-overexpressing cultured hippocampal neurons was compared to the profile of the corresponding control populations. (neurons expressing GFP). Neurogenin3, a proneural transcription factor controlled by Notch receptor, is involved in hippocampal neuron differentiation and synapses, but little is known about the molecular bases of Ngn3 activity in neurons. Microarray analysis indicated that overexpression of Ngn3 upregulated a number of genes related with cytoskeleton dynamics. One of then was Fmn1 whose protein is associated with actin and microtubule cytoskeleton. Overexpression of the isoform Fmn1-Ib in cultured hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs without affecting GABAergic synapses resulting in a modification in the balance between excitation and inhibition. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritic and synaptic plasticity as a key protein in the Nng3 signaling pathway that contributes to understanding of molecular mechanisms of the neuronal differentiation. Cultured hippocampal neurons were transduced using Sindbis virus bearing myc-tagged Ngn3 or GFP as control. Cells were lysed and total RNA was extracted.Gene expression profiles were obtained for each sample and compared
2011-01-27 | E-GEOD-26911 | biostudies-arrayexpress
Project description:Synapse formation is critical for the wiring of neural circuits in the developing brain. The synaptic scaffolding protein S-SCAM/MAGI-2 has important roles in the assembly of signaling complexes at postsynaptic densities. However, the role of S-SCAM in establishing the entire synapse is not known. Here, we report significant effects of RNAi-induced S-SCAM knockdown on the number of synapses in early stages of network development in vitro. In vivo knockdown during the first three postnatal weeks reduced the number of dendritic spines in the rat brain neocortex. Knockdown of S-SCAM in cultured hippocampal neurons severely reduced the clustering of both pre- and postsynaptic components. This included synaptic vesicle proteins, pre- and postsynaptic scaffolding proteins, and cell adhesion molecules, suggesting that entire synapses fail to form. Correspondingly, functional and morphological characteristics of developing neurons were affected by reducing S-SCAM protein levels: neurons displayed severely impaired synaptic transmission and reduced dendritic arborization. A next generation sequencing approach showed normal expression of housekeeping genes, but changes of expression levels in 39 synaptic signaling molecules in cultured neurons. These results indicate that S-SCAM mediates the recruitment of all key classes of synaptic molecules during synapse assembly and is critical for the development of neural circuits in the developing brain.
2023-10-02 | GSE228093 | GEO