Proteomic profiling of sclerosis hippocampus revealed dysregulated packaging of vesicular neurotransmitters in temporal lobe epilepsy
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Brain, Neutrophil
DISEASE(S): Temporal Lobe Epilepsy
SUBMITTER: 
Wei Ge
LAB HEAD: Wei Ge
PROVIDER: PXD010544 | Pride | 2020-07-17
REPOSITORIES: Pride
Publications
Proteomic profiling of sclerotic hippocampus revealed dysregulated packaging of vesicular neurotransmitters in temporal lobe epilepsy.
Zhang Yusheng Y Liu Yifan Y Jia Yangjie Y Zhao Yuming Y Ma Chao C Bao Xinjie X Meng Xianbin X Dou Wanchen W Wang Xia X Ge Wei W
Epilepsy research 20200701
<h4>Purpose</h4>Temporal lobe epilepsy (TLE) is the most common type of epilepsy. Hippocampal sclerosis is the most distinctive pathological feature of TLE; however, its role in the pathogenesis of TLE remains to be clarified. We performed global protein expression analysis of hippocampus from TLE patients and controls, aiming to reveal the molecular signaling pathways related to TLE.<h4>Method</h4>Proteomic and bioinformatic analyses of the hippocampus were performed on 4 TLE and 4 control samp ...[more]
Similar Datasets
Project description:Proteomics and bioinformatic analyses of hippocampus were performed. High-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with TMT-6plex quantification, was applied for global protein expression analysis. The proteomics results were validated by Western blot analysis.
2020-07-17 | PXD010543 | Pride
Project description:The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Teadresponsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosagedependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson’s chorioretinal atrophy and congenital retinal coloboma. 60 pooled eyes from 36 hpf wild type or vsx2:Gal4/dsRed:14xUAS:YapS87A embryos were pooled for one sample. Three wild type and three vsx2:Gal4/dsRed:14xUAS:YapS87A pools were analyzed for RNA.
2015-08-06 | E-GEOD-71681 | biostudies-arrayexpress
Project description:In order to disclose the mechanisms, a high-throughput quantitative proteomics analysis was established to investigate the proteome profiles changes of hippocampus and temporal lobe of WT mice, APP/PS1 mice and rapamycin treated APP/PS1 mice.The extraction of proteins of hippocampus and temporal tissue employed liquid nitrogen grounding method, which was described as previous works of our laboratory and other laboratories [20, 21]. After fully and immediately grinding under the protection of liquid nitrogen, the products was dissolved by lysis buffer (8 M urea and 1 cocktail in PBS, pH = 8.0) prepared in ice ahead of schedule and then the solutions were transferred to a 1.5-mL tube in ice. Cellular debris was removed by centrifugation (12,000 rpm, 15 min, 4 °C) and the liquid supernatant was transferred into a fresh 1.5-mL tube and immediately stored at -80 °C. The protein concentration of the supernatant was detected by Nanodrop 2000 (Thermo Scientific, NJ, USA) following the manufacture instructions.
2019-02-28 | PXD009540 | Pride
Project description:Parkinson's disease (PD) listed as the second most common neurodegenerative disease. 2-[[(1,1-Dimethylethyl)oxidoimino]-methyl]-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has shown benefits for the treatment both in vitro and in vivo, TBN protects and rescues dopaminergic neurons from MPP(+) and MPTP/6-OHDA-induced damage by reducing ROS and increasing cellular antioxidative defense capability. Here, we investigate the proteome changes in the 6-OHDA induced PD rat model and the rescue effects after treated by TBN.
2022-03-02 | PXD004812 | Pride
Project description:Fragile X syndrome (FXS), the leading cause of inherited form of mental retardation and autism, is caused by the transcriptional silencing of fmr1 encoding the protein of FMRP. FMRP, acting as an RNA binding protein, FMRP is a wide expressed protein, but primarily in the brain and testis and can regulate approximately 4% of transcripts. Macroorchidism is one of the common symptoms observed both in the FXS people and mice. Thus, we analyzed the protein profiles of cerebral cortex, hippocampus and testis from both the fmr1-KO and WT mouse using a quantitative proteomics. Proteins (FMRP, RS8, RL23A and MPZ) identified by MS/MS were also verified by Western blot. Among the identified proteins, most of the significant changed proteins were downregulated in the FMRP absence. The Gene Ontology and pathway analysis revealed that the changed proteins were clustered in polyribosome and RNA binding proteins in both cerebral cortex and hippocampus, but not the same in testis. Our results provide detailed insights to the ribosome protein profiles of cerebral cortex, hippocampus and testis in the absence of FMRP. Our studies also give a better understanding of protein profile changes and underling dysregulated pathways arising from the fmr1 silencing in the FXS.
2022-02-28 | PXD005089 | Pride
Project description:The purpose of this study was to investigate whether expression of specific genes in peripheral blood can be used as surrogate marker(s) to detect and distinguish target organ-specific chemical toxicity in rats. Rats were intraperitoneally administered a single, acute dose of a well-established hepatotoxic (acetaminophen) or neurotoxic (methyl parathion) chemical. Administration of acetaminophen (AP) or methyl parathion (MP) in the rats resulted in hepatotoxicity as evidenced from elevated blood transaminase activities or neurotoxicity as evidenced from the inhibition of acetyl cholinesterase activity in the blood, respectively. Microarray analysis of the global gene expression profile of rat blood identified distinct gene expression markers capable of detecting and distinguishing hepatotoxicity and neurotoxicity induced by AP and MP, respectively. Differential expressions of the marker genes specific for hepatotoxicity and neurotoxicity were detectable in the blood much earlier than the appearance of the commonly used clinical markers, serum transaminases and acetyl cholinesterase. In summary, our results demonstrated that blood gene expression markers can detect and distinguish target organ toxicity non-invasively and with higher sensitivity than traditional surrogate markers. Keywords: blood, acetaminophen, methyl parathion, rat, hepatotoxicity, neurotoxicity 38 samples were analyzed in this experiment. 15 rats were intraperitoneally administered acetaminophen (AP), 15 rats were intraperitoneally administered methyl parathion (MP), and 8 rats were intraperitoneally administered vegetable oil. At time intervals of 4, 12, and 24 hours following administration of acetaminophen or methyl parathion, 4 rats per chemical were sacrificed and blood was collected. At the 168-hour time interval, 3 rats per chemical were sacrificed and blood was collected. The control animals were sacrificed at the 24-hour time interval. Therefore, there were four rats in each of the 4-, 12-, and 24-hour time points for each chemical and four control rats for each chemical. Similarly, there were three rats in the 168-hour time interval for each chemical. The groups for each chemical and time interval are labeled as follows: APâcontrolâ4 rats: blood_AP_0_4, blood_AP_0_5, blood_AP_0_33, and blood_AP_0_34 APâ4-hoursâ4 rats: blood_AP_4_35, blood_AP_4_38, blood_AP_4_39, and blood_AP_4_40 APâ12-hoursâ4 rats: blood_AP_12_41, blood_AP_12_42, blood_AP_12_43, and blood_AP_12_45 APâ24-hoursâ4 rats: blood_AP_24_47, blood_AP_24_48, blood_AP_24_49, and blood_AP_24_51 APâ168-hoursâ3rats: blood_AP_168_53, blood_AP_168_54, and blood_AP_168_56 MPâcontrolâ4 rats: blood_MP_0_1, blood_MP_0_2, blood_MP_0_3, and blood_MP_0_ 31 MPâ4-hoursâ4 rats: blood_MP_4_11, blood_MP_4_12, blood_MP_4_13, and blood_MP_4_22 MPâ12-hoursâ4 rats: blood_MP_12_20, blood_MP_12_23, blood_MP_12_24, and blood_MP_12_25 MPâ24-hoursâ4 rats: blood_MP_24_6, blood_MP_24_7, blood_MP_24_9, and blood_MP_24_21 MPâ168-hoursâ3rats: blood_MP_168_26, blood_MP_168_27, and blood_MP_168_29
2010-04-08 | E-GEOD-13442 | biostudies-arrayexpress
Project description:Introduction: The relationship between epilepsy and cognitive dysfunction has been investigated in canines, and memory impairment was prevalent in dogs with epilepsy. There is some evidence that canines with epilepsy have greater amyloid-β (Aβ) accumulation and neuronal degeneration than healthy controls. The present study investigated plasma Aβ42 levels and performed proteomic profiling in dogs with refractory epilepsy and healthy dogs. Methods: In total, eight dogs, including four healthy dogs and four dogs with epilepsy, were included in the study. Blood samples were collected to analyze Aβ42 levels and perform proteomic profiling. Changes in the plasma proteomic profiles of dogs were determined by nano LC-MS/MS. Results and discussion: The plasma Aβ42 level was significantly higher in dogs with epilepsy (99 pg/mL) than in healthy dogs (5.9 pg/mL). In total, 155 proteins were identified, and of these, the expression of 40 proteins was altered in epilepsy. Among these proteins, which are linked to neurodegenerative diseases, 10 (25%) were downregulated in dogs with epilepsy, whereas 12 (30%) were upregulated. The expression of the acute phase proteins haptoglobin and α2-macroglobulin significantly differed between the groups. Complement factor H and ceruloplasmin were only detected in epilepsy dogs, suggesting that neuroinflammation plays a role in epileptic seizures. Gelsolin, which is involved in cellular processes and cytoskeletal organization, was only detected in healthy dogs. Gene Ontology annotation revealed that epilepsy can potentially interfere with biological processes, including cellular processes, localization, and responses to stimuli. Seizures compromised key molecular functions, including catalytic activity, molecular function regulation, and binding. Defense/immunity proteins were most significantly modified during the development of epilepsy. In Kyoto Encyclopedia of Genes and Genomes pathway analysis, complement and coagulation cascades were the most relevant signaling pathways affected by seizures. The findings suggested that haptoglobin, ceruloplasmin, α2-macroglobulin, complement factor H, and gelsolin play roles in canine epilepsy and Aβ levels based on proteomic profiling. These proteins could represent diagnostic biomarkers that, after clinical validation, could be used in veterinary practice as well as proteins relevant to disease response pathways. To determine the precise mechanisms underlying these relationships and their implications in canine epilepsy, additional research is required.
2023-12-12 | PXD043962 | Pride
Project description:Ion channel splice array data collected from temporal neocortex brain tissue collected from patients with mesial temporal lobe epilepsy. Temporal cortex samples from control subjects were compared to temporal neocortex of patients with mesial temporal lobe epilepsy
2010-06-11 | E-GEOD-6773 | biostudies-arrayexpress
Project description:Global expression profiling of epileptogenesis has been confounded by variability across laboratories, epilepsy models, tissue sampled and experimental platforms, with the result that very few genes demonstrate consistent expression changes. The present study minimizes these confounds by combining Affymetrix microarray datasets from seven laboratories, using three status epilepticus (SE) models of epilepsy in rats (pilocarpine, kainate, self-sustained SE or SSSE) and the rat kindling model. Total RNA was harvested from laser-captured dentate granule cells from 6 rats at three times during the early-to-mid latent phase that precedes epilepsy symptoms in the SE models (1, 3 and 10 days after SE), or 24 hr after the first stage 2, stage 4 and stage 5 seizure in the kindling model. Each epilepsy model was studied in two independent laboratories except SSSE. The initial goals of this study were to a) identify model-independent transcriptional changes in dentate granule cells that could point to novel intervention targets for epileptogenesis, b) characterize the basal transcriptional profile of dentate granule cells, and c) identify genes that have highly variable expression. Each experimental group consists of 6 rats (biological replicates) from one laboratory at a single time point, except for the SSSE group (6 at day 1 after SSSE, 5 controls and at day 3 after SSSE, 4 at day 10). Thus granule cells were harvested from 164 rats.
2013-06-08 | E-GEOD-47752 | biostudies-arrayexpress
Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment
2012-12-01 | E-GEOD-25453 | biostudies-arrayexpress