Peripheral Blood Mononuclear Transcriptomics Identifies Distinct Acute and Delayed Molecular Biomarkers in the Pilocarpine Model of Temporal Lobe Epilepsy
Abstract number :
1.006
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2022
Submission ID :
2204776
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Claudia Espinosa-Garcia, PhD – Emory University; Asheebo Rojas, PhD – Instructor, Pharmacology and Chemical Biology, Emory University; Hailian Xiao, BS – Neurology – Emory University; Young Lin, Undergrad student – Neurology – Emory University; Aditya Natu, MS in Bioinformatics – Emory University; Alejandra Valdivia, PhD – Medicine – Emory University; Raymond Dingledine, PhD – Professor and Chair, Pharmacology and Chemical Biology, Emory University; Srikant Rangaraju, MBBS, MS – Associate Professor, Neurology, Emory University
Rationale: Neuroinflammation is a key pathophysiological hallmark of neurological diseases. In epilepsy, the brain inflammatory response is characterized by an acute glial activation, which persists overtime as a result of recurrent seizures. Similarly, peripheral immune cells become activated and release proinflammatory mediators, which enter the brain and propagate inflammation. The 2021 AES/NINDS Epilepsy Research Benchmarks emphasized the need for biomarkers to identify, predict, and monitor epileptogenesis and disease progression. Our hypothesis is that a time course study of peripheral immune transcriptome profiles might reveal new biomarkers that can be useful in the prevention and treatment of epilepsy.
Methods: In the current study, we used the pilocarpine-induced status epilepticus (SE) in rats, a well-validated model of temporal lobe epilepsy; non-seizure controls received saline. Cohorts of rats (n=4) were euthanized at 1, 3, 7, 14 and 28 days post-SE, these time points correspond to the acute, latent, and chronic phases of epileptogenesis. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using Ficoll density gradient centrifugation, total RNA was isolated with TRIzol, and transcriptome profiles were assessed by RNA sequencing. For differential expression analysis, between non-seizure controls and SE rats at different epileptogenesis stages, we used the DESeq2 software. Genes exhibiting log2(fold change) > 1 or log2(fold change) < -1 with adjusted p-value < 0.05 were identified as significant.
Basic Mechanisms