scholarly journals The circadian dynamics of the hippocampal transcriptome and proteome is altered in experimental temporal lobe epilepsy

2020 ◽  
Vol 6 (41) ◽  
pp. eaat5979
Author(s):  
K. J. Debski ◽  
N. Ceglia ◽  
A. Ghestem ◽  
A. I. Ivanov ◽  
G. E. Brancati ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Aerobic Glycolysis ◽  
Time Dependent ◽  
Experimental Epilepsy ◽  
Protein Expressions ◽  
Drug Treatments

Gene and protein expressions display circadian oscillations, which can be disrupted in diseases in most body organs. Whether these oscillations occur in the healthy hippocampus and whether they are altered in epilepsy are not known. We identified more than 1200 daily oscillating transcripts in the hippocampus of control mice and 1600 in experimental epilepsy, with only one-fourth oscillating in both conditions. Comparison of gene oscillations in control and epilepsy predicted time-dependent alterations in energy metabolism, which were verified experimentally. Although aerobic glycolysis remained constant from morning to afternoon in controls, it increased in epilepsy. In contrast, oxidative phosphorylation increased in control and decreased in epilepsy. Thus, the control hippocampus shows circadian molecular remapping, which is altered in epilepsy. We suggest that the hippocampus operates in a different functioning mode in epilepsy. These alterations need to be considered when studying epilepsy mechanisms, designing drug treatments, and timing their delivery.

scholarly journals Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

2013 ◽  
Vol 7 ◽  
Author(s):  
Pierangelo Cifelli ◽  
Eleonora Palma ◽  
Cristina Roseti ◽  
Gianluca Verlengia ◽  
Michele Simonato
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Drug Treatments

Time-dependent evolution of seizures in a model of mesial temporal lobe epilepsy

2017 ◽  
Vol 106 ◽  
pp. 205-213 ◽  
Author(s):  
Charles Behr ◽  
Maxime Lévesque ◽  
Thomas Stroh ◽  
Massimo Avoli
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Mesial Temporal Lobe Epilepsy ◽  
Time Dependent ◽  
Mesial Temporal Lobe

scholarly journals Spatio-temporal heterogeneity in hippocampal metabolism in control and epilepsy conditions

2020 ◽  
Author(s):  
Giulio E. Brancati ◽  
Chahinaz Rawas ◽  
Antoine Ghestem ◽  
Christophe Bernard ◽  
Anton I. Ivanov
Keyword(s):  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Energy Production ◽  
Cell Function ◽  
Dorsal Hippocampus ◽  
Aerobic Glycolysis ◽  
Ventral Hippocampus ◽  
Temporal Organization ◽  
Metabolic Imaging ◽  
Spatio Temporal

ABSTRACTEnergy production, mostly via glycolysis and oxidative phosphorylation, which is at the core of cell function, varies in a circadian manner. Whether energy production is tailored to the functional needs of the networks remains poorly understood. The dorsal and ventral part of the hippocampus are involved in different functional circuits. Using metabolic imaging and metabolite sensing, we show that the ventral hippocampus favors aerobic glycolysis over oxidative phosphorylation as compared to the dorsal part in the morning. However, in the afternoon, aerobic glycolysis is decreased and oxidative phosphorylation increased in the ventral hippocampus. In the dorsal hippocampus, the metabolic activity varies less between these two times but is still weaker than in the ventral. Thus, energy metabolism is different in space (along the dorso-ventral axis) and time (in a circadian manner) in the hippocampus. A similar analysis in an experimental model of epilepsy revealed a large alteration of such spatio-temporal organization. In addition to a general hypometabolic state, the spatial difference disappeared in the morning, when seizure probability is low. In the afternoon, when seizure probability is high, the aerobic glycolysis was enhanced in both parts but this increase was stronger in the ventral area. We suggest that energy metabolism is tailored to the functions performed by brain networks, which vary in space and time. In pathological conditions, the alterations of these general rules may contribute to network dysfunctions.

scholarly journals Spatio-temporal heterogeneity in hippocampal metabolism in control and epilepsy conditions

2021 ◽  
Vol 118 (11) ◽  
pp. e2013972118
Author(s):  
Giulio E. Brancati ◽  
Chahinaz Rawas ◽  
Antoine Ghestem ◽  
Christophe Bernard ◽  
Anton I. Ivanov
Keyword(s):  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Energy Production ◽  
Dorsal Hippocampus ◽  
Ex Vivo ◽  
Aerobic Glycolysis ◽  
Metabolic Imaging ◽  
Hypometabolic State ◽  
Spatio Temporal ◽  
Night And Day

The hippocampus’s dorsal and ventral parts are involved in different operative circuits, the functions of which vary in time during the night and day cycle. These functions are altered in epilepsy. Since energy production is tailored to function, we hypothesized that energy production would be space- and time-dependent in the hippocampus and that such an organizing principle would be modified in epilepsy. Using metabolic imaging and metabolite sensing ex vivo, we show that the ventral hippocampus favors aerobic glycolysis over oxidative phosphorylation as compared to the dorsal part in the morning in control mice. In the afternoon, aerobic glycolysis is decreased and oxidative phosphorylation increased. In the dorsal hippocampus, the metabolic activity varies less between these two times but is weaker than in the ventral. Thus, the energy metabolism is different along the dorsoventral axis and changes as a function of time in control mice. In an experimental model of epilepsy, we find a large alteration of such spatiotemporal organization. In addition to a general hypometabolic state, the dorsoventral difference disappears in the morning, when seizure probability is low. In the afternoon, when seizure probability is high, the aerobic glycolysis is enhanced in both parts, the increase being stronger in the ventral area. We suggest that energy metabolism is tailored to the functions performed by brain networks, which vary over time. In pathological conditions, the alterations of these general rules may contribute to network dysfunctions.

scholarly journals Involvement of GluA1-AMPAR-mediated LTP in time-dependent decline of cognitive function in rats with temporal lobe epilepsy

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Xiaoqing Luo ◽  
Xiaoli Yu ◽  
Jufang Liang ◽  
Ruidi Sun ◽  
Cheng Li ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Temporal Lobe Epilepsy ◽  
Learning And Memory ◽  
Western Blotting ◽  
Temporal Lobe ◽  
Long Term Potentiation ◽  
Time Dependent ◽  
Dependent Manner ◽  
Behavioral Tests

Abstract Background Cognitive impairment is one of the common comorbidities in patients with temporal lobe epilepsy (TLE), but the underlying mechanisms remain largely unknown. Previous studies have found significant decay of hippocampal long-term potentiation (LTP) in TLE rats with cognitive impairment. As the activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is responsible for LTP formation and learning and memory, we investigated whether AMPARs are involved in the LTP inhibition and the TLE-associated cognitive impairments. Methods TLE rat model was established by intraperitoneal injection of lithium chloride-pilocarpine on postnatal day 21 (P21). Learning and memory performance, hippocampal expression of membrane GluA1-AMPARs, and hippocampal LTP were tested by behavioral tests, western blotting, and field potential recording, respectively, at 1, 5 and 13 weeks after induction of status epilepticu (SE). Finally, the effects of (S)-AMPA, an agonist of AMPARs, on LTP and cognitive function were tested. Results Results of behavioral tests revealed an time-dependent decline in the learning and memory of TLE rats when compared to the age-matched controls at week 5 and 13, rather than at week 1 after the induction of SE. Western blotting showed that the hippocampal expression of membrane GluA1 was significantly decreased in a time-dependent manner in the TLE rats when compared to the age-matched controls at weeks 5 and 13, rather than at week 1 after the induction of SE. Similarly, the hippocampal LTP was inhibited in a time-dependent manner in TLE rats at weeks 5 and 13, rather than at week 1 after the induction of SE. Moreover, intra-hippocampal injection of (S)-AMPA ameliorated the deficits in learning as well as spatial and emotional memory in a dose-dependent manner, and partially reversed the inhibition of CA1 LTP in the TLE rats at week 13 after the induction of SE. Conclusions The reduced expression of hippocampal membrane GluA1 may be involved in LTP decay in CA1 and cognition impairment in TLE rats.

scholarly journals iTRAQ-Based Proteomic Analysis of Dentate Gyrus in Temporal Lobe Epilepsy With Hippocampal Sclerosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenbiao Xiao ◽  
Zhiquan Yang ◽  
Xiaoxin Yan ◽  
Li Feng ◽  
Lili Long ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Temporal Lobe Epilepsy ◽  
Dentate Gyrus ◽  
Temporal Lobe ◽  
Molecular Mechanisms ◽  
Focal Epilepsy ◽  
Hippocampal Sclerosis ◽  
Interaction Network ◽  
Absolute Quantitation ◽  
Functional Changes

Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment, and mostly presents with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis (HS). However, the underlying molecular mechanisms involved remain poorly characterized. The dentate gyrus (DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, a isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technique was performed for the analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from autopsy. Our proteomic data identified 5,583 proteins, of which 82 proteins were upregulated and 90 proteins were downregulated. Bioinformatics analysis indicated that differentially expressed proteins were enriched in “synaptic vesicle,” “mitochondrion,” “cell-cell adhesion,” “regulation of synaptic plasticity,” “ATP binding,” and “oxidative phosphorylation.” Protein-protein interaction network analysis found a pivotal module of 10 proteins that were related to “oxidative phosphorylation.” This study has investigated proteomic alterations in the DG region of TLE-HS patients, and paved the way for the better understanding of epileptogenesis mechanisms and future therapeutic intervention.

Theory of mind and social competence in children and adolescents with temporal lobe epilepsy.

2019 ◽  
Vol 33 (7) ◽  
pp. 986-995 ◽  
Author(s):  
Elizabeth Stewart ◽  
Cathy Catroppa ◽  
Linda Gonzalez ◽  
Deepak Gill ◽  
Richard Webster ◽  
...  
Keyword(s):  
Theory Of Mind ◽  
Social Competence ◽  
Temporal Lobe Epilepsy ◽  
Children And Adolescents ◽  
Temporal Lobe

Decreased Dopamine D2/D3-Receptor Binding in the Temporal Lobe and the Bilateral Basal Ganglia in patients with Temporal Lobe Epilepsy

2012 ◽  
Vol 43 (01) ◽  
Author(s):  
VE Bernedo Paredes ◽  
H Schwartz ◽  
M Gartenschläger ◽  
M Gartenschläger ◽  
HG Buchholz ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Receptor Binding ◽  
D3 Receptor ◽  
Dopamine D2
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