Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptional profiling of dentate granule cells in 4 rat epilepsy models

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Winnie Liang

PROVIDER: E-GEOD-47752 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

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Transcriptional profiling of dentate granule cells in 4 rat epilepsy models

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