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Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

ABSTRACT: PURPOSE:The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. PROCEDURES:Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n?=?5) or kainic acid (5 mg/kg/injection, epileptic group, n?=?15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. RESULTS:Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p?

SUBMITTER: Serrano ME

PROVIDER: S-EPMC7497718 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Exploring with [<sup>18</sup>F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

Serrano Maria Elisa ME Bahri Mohamed Ali MA Becker Guillaume G Seret Alain A Germonpré Charlotte C Lemaire Christian C Giacomelli Fabrice F Mievis Frédéric F Luxen André A Salmon Eric E Rogister Bernard B Raedt Robrecht R Plenevaux Alain A

Molecular imaging and biology 20201001 5

<h4>Purpose</h4>The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model.<h4>Procedures</h4>Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE ...[more]

PMID: 32206990

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Project description:Mesial Temporal Lobe Epilepsy (MTLE) is a chronic disease characterized by recurrent unprovoked partial seizures. Current treatments lack long-term efficacy and typically act only to ameliorate the symptomology, rather than to modify the course of the disease. Chronic kainic acid (KA)-induced models of MTLE mimic prominent histopathological and electroencephalographic features of human MTLE, including hippocampal sclerosis, CA1 neuronal loss, astrogliosis, microgliosis, and electrographic hippocampal discharges. Here we examined the transcriptional profiles of the hippocampus of KA - vs sham-injected mice from epileptogenesis to the stabilization of spontaneous recurring seizures. KA (1 nmol) or saline (sham) was injected unilaterally into the dorsal hippocampus of 12 week old C57BL/6J mice, and the ipsilateral (IL) and contralateral (CL) hippocampi were isolated for whole-genome expression profiling (Illumina microarray) or immunohistochemistry 7, 28 and 60 d later. Differential gene expression analysis of the IL hippocampus indicated that 1349, 484, and 439 genes were significantly (fdr<0.05) altered in KA compared to sham at 7, 28 and 60 d, respectively. 108 genes were altered at all time-points assessed, while others were altered in a time-dependent manner, indicative of distinct hippocampal gene expression profiles across the course of disease. Ingenuity Pathway Analysis revealed that specific immune cell and inflammatory signaling pathways were upregulated at 7 and 28 d, in support of a role of neuroinflammation in the disease etiology. The top canonical pathways profile at 60 d was quite distinct from that at 7 and 28 d, although certain inflammatory pathways were still prevalent, indicative of pathways involved in the maintenance of the disease. Consistent with a role of neuroinflammation in MTLE, immunohistochemical analyses demonstrated time-dependent changes in both the intensity of immunoreactivity and number of Iba1- and GFAP-positive cells. To reveal gene networks not apparent with differential expression data alone, weighted gene co-expression analysis (WGCNA) was performed. A gene network that highly associated with 7 d IL-KA (but not 28 and 60 d) was identified, which may point to changes involved in the process of epileptogenesis. Another gene network revealed a group of genes highly associated with changes occurring at 28 and 60 d, but not 7 d, which may point to molecules involved in the generation of spontaneous recurring seizures. Collectively, results indicate that specific pathways, including many associated with neuroinflammation, are activated in a time-dependent manner in MTLE.

Dataset Information

Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

Publications

Exploring with [<sup>18</sup>F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.

Similar Datasets

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