scholarly journals Decreased expression of the clock gene Bmal1 is involved in the pathogenesis of temporal lobe epilepsy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hao Wu ◽  
Yong Liu ◽  
Lishuo Liu ◽  
Qiang Meng ◽  
Changwang Du ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Clock Gene ◽  
High Throughput Sequencing ◽  
Clock Genes ◽  
Hippocampal Sclerosis ◽  
Control Group ◽  
Type I ◽  
Sequencing Analysis ◽  
Clock Proteins

AbstractClock genes not only regulate the circadian rhythm of physiological activities but also participate in the pathogenesis of many diseases. Previous studies have documented the abnormal expression of clock genes in epilepsy. However, the molecular mechanism of brain and muscle Arnt-like protein 1 (Bmal1), one of the core clock genes, in the epileptogenesis and seizures of temporal lobe epilepsy (TLE) remain unclear. We first investigated the levels of Bmal1 and other clock proteins in the hippocampus of subjects with epilepsy to define the function of Bmal1. The levels of Bmal1 were decreased during the latent and chronic phases in the experimental group compared with those in the control group. Knockout of Bmal1 in hippocampal dentate gyrus (DG) neurons of Bmal1flox/flox mice by Synapsin 1 (Syn1) promoter AAV (adeno-associated virus) lowered the threshold of seizures induced by pilocarpine administration. High-throughput sequencing analysis showed that PCDH19 (protocadherin 19), a gene associated with epilepsy, was regulated by Bmal1. PCDH19 expression was also decreased in the hippocampus of epileptic mice. Furthermore, the higher levels of Bmal1 and PCDH19 were detected in patients with no hippocampal sclerosis (no HS) than in patients with HS International League Against Epilepsy (ILAE) type I and III. Altogether, these data suggest that decreased expression of clock gene Bmal1 may participate in epileptogenesis and seizures via PCDH19 in TLE.

scholarly journals Decreased Clock Gene Bmal1 Mediates Epileptogenesis via PCDH19 in Temporal Lobe Epilepsy

2020 ◽  
Author(s):  
Hao Wu ◽  
Yong Liu ◽  
Lishuo Liu ◽  
Qiang Meng ◽  
Changwang Du ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Clock Gene ◽  
High Throughput Sequencing ◽  
Clock Genes ◽  
Hippocampal Sclerosis ◽  
Control Group ◽  
Type I ◽  
Sequencing Analysis ◽  
Clock Proteins

Abstract Clock genes not only regulate the circadian rhythm of physiological activities but also participate in the pathogenesis of many diseases. Previous studies have found the abnormal expression of clock genes in epilepsy. However, as the core clock gene, the molecular mechanism of Bmal1 in the epileptogenesis and seizures of temporal lobe epilepsy (TLE) is still unclear. To define the function of Bmal1, we firstly investigated the levels of Bmal1 and other clock proteins in the hippocampus in epilepsy. In the latency and chronic phases, the levels of Bmal1 were decreased compared with the control group. Knockout of Bmal1 in hippocampal dentate gyrus (DG) neurons of Bmal1flox/flox mice by Synapsin 1 (Syn1) promoter AAV (adeno-associated virus) lowered the threshold of seizures induced by pilocarpine administration. High throughput sequencing analysis showed that PCDH19 (protocadherin 19), a gene associated with epilepsy, was regulated by Bmal1. And the expression of PCDH19 was also decreased in the hippocampus of epileptic mice. Furthermore, the levels of Bmal1 and PCDH19 were higher in the patients with no hippocampal sclerosis (no HS), compared to HS International League Against Epilepsy (ILAE) type I and III. Altogether, these data suggest that decreased expression of clock gene Bmal1 may participate in the epileptogenesis and seizures via PCDH19 in TLE.

scholarly journals Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

2021 ◽  
Vol 22 (8) ◽  
pp. 3860
Author(s):  
Elisa Ren ◽  
Giulia Curia
Keyword(s):  
Animal Models ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Current Knowledge ◽  
Focal Epilepsy ◽  
Ex Vivo ◽  
Hippocampal Sclerosis ◽  
Control Group ◽  
Epileptogenic Zone ◽  
Epileptiform Discharges

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

scholarly journals Apoptosis through Death Receptors in Temporal Lobe Epilepsy-Associated Hippocampal Sclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Marcelo Ananias Teocchi ◽  
Lília D’Souza-Li
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Death Receptor ◽  
Death Receptors ◽  
Control Group ◽  
Extrinsic Pathway ◽  
Seizure Models ◽  
Pharmacological Studies ◽  
Encoding Genes

Seizure models have demonstrated that neuroinflammation and neurodegeneration are preponderant characteristics of epilepsy. Considering the lack of clinical studies, our aim is to investigate the extrinsic pathway of apoptosis in pharmacoresistant temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients, TLE(HS). By a specific death receptor-mediated apoptosis array plate, 31 upregulated targets were revealed in the sclerotic hippocampus from TLE(HS) patients. Amongst them are the encoding genes for ligands (FASLG,TNF,andTNFSF10) and death receptors (FAS,TNFRSF1A,TNFRSF10A,andTNFRSF10B). In addition, we evaluated the hippocampal relative mRNA expression of the two TNF receptors,TNFRSF1AandTNFRSF1B, in patients, being both upregulated (n=14;P<0.01andP<0.04, resp.) when compared to thepost mortemcontrol group (n=4). Our results have clearly suggested that three different death receptor apoptotic systems may be associated with the maintenance and progression of TLE-associated HS: (1) TNF-TNFRSF1A, (2) FASLG-FAS, and (3) TNFSF10-TNFRSF10A/B. Their effects on epilepsy are still scarcely comprehended. Our study points out to TNF and TNF receptor superfamily pathways as important targets for pharmacological studies regarding the benefits of an anti-inflammatory therapy in these patients.

scholarly journals Stereotactic EEG-guided radiofrequency thermocoagulation versus anterior temporal lobectomy for mesial temporal lobe epilepsy with hippocampal sclerosis: study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yi-He Wang ◽  
Si-Chang Chen ◽  
Peng-Hu Wei ◽  
Kun Yang ◽  
Xiao-Tong Fan ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Controlled Trial ◽  
Mesial Temporal Lobe Epilepsy ◽  
Temporal Lobectomy ◽  
Anterior Temporal Lobectomy ◽  
Radiofrequency Thermocoagulation ◽  
Mesial Temporal Lobe ◽  
Randomised Controlled

Abstract Introduction In this report, we aim to describe the design for the randomised controlled trial of Stereotactic electroencephalogram (EEG)-guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE. Methods and analysis STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is the cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes. Discussion SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual field protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide higher levels of clinical evidence for the treatment of mTLE. Trial registration ClinicalTrials.gov NCT03941613. Registered on May 8, 2019. The STARTS protocol has been registered on the US National Institutes of Health. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.

A pioneering FreeSurfer volumetric study of a series of patients with mesial temporal lobe epilepsy and hippocampal sclerosis with comorbid depression

2021 ◽  
pp. 111281
Author(s):  
Nathália Stela Visoná de Figueiredo ◽  
Larissa Botelho Gaça ◽  
Idaiane Batista Assunção-Leme ◽  
Lenon Mazetto ◽  
Maria Teresa Fernandes Castilho Garcia ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Mesial Temporal Lobe Epilepsy ◽  
Comorbid Depression ◽  
Volumetric Study ◽  
Mesial Temporal Lobe

scholarly journals Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery

Seizure ◽  
2017 ◽  
Vol 48 ◽  
pp. 74-78 ◽  
Author(s):  
Sara Casciato ◽  
Angelo Picardi ◽  
Alfredo D’Aniello ◽  
Marco De Risi ◽  
Giovanni Grillea ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Hippocampal Sclerosis ◽  
Seizure Outcome ◽  
Temporal Pole
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