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1. Animal Models of Febrile Seizures: Limitations and Recent Advances in the Field.

Author

Griflyuk, Alexandra V., Postnikova, Tatyana Y., and Zaitsev, Aleksey V.

Subjects
FEBRILE seizures, NEURAL development, ANIMAL models for aging, NERVOUS system, NEUROLOGICAL disorders
Abstract

Febrile seizures (FSs) are defined as seizures occurring in children aged 6 months to 5 years with a background of elevated body temperature. It is one of the most common neurological disorders of childhood, emphasizing the importance of understanding the causes of FSs and their impact on the developing nervous system. However, there are significant limitations to the technologies currently available for studying the etiology and pathophysiology of seizures in humans. It is currently not possible to adequately capture the subtle molecular and structural rearrangements of the nervous system that can occur after seizures in humans. The use of animal models can be invaluable for these purposes. The most commonly used models in modern research are hyperthermic models in rats and mice aged 10–12 days. While these models can reproduce many of the characteristics of FSs, they have certain limitations. This review outlines the key considerations when working with models of FSs, provides an overview of current approaches to producing seizures in different model subjects, and presents a summary of key findings regarding morphological and functional changes in the brain and behavioral alterations that have been identified in studies using animal models of FSs. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Identification of Reliable Reference Genes for Use in Gene Expression Studies in Rat Febrile Seizure Model.

Author

Kovalenko, Anna A., Zakharova, Maria V., Schwarz, Alexander P., Zubareva, Olga E., and Zaitsev, Aleksey V.

Subjects
REVERSE transcriptase polymerase chain reaction, GENE expression, FEBRILE seizures, PREFRONTAL cortex, BRAIN anatomy
Abstract

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To ensure the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression levels were Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model. [ABSTRACT FROM AUTHOR]

Published
2024
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3. PPARβ/δ Agonist GW0742 Modulates Microglial and Astroglial Gene Expression in a Rat Model of Temporal Lobe Epilepsy.

Author

Zubareva, Olga E., Kharisova, Adeliya R., Roginskaya, Anna I., Kovalenko, Anna A., Zakharova, Maria V., Schwarz, Alexander P., Sinyak, Denis S., and Zaitsev, Aleksey V.

Subjects
TEMPORAL lobe epilepsy, LABORATORY rats, PEROXISOME proliferator-activated receptors, GENE expression, GENETIC regulation
Abstract

The role of astroglial and microglial cells in the pathogenesis of epilepsy is currently under active investigation. It has been proposed that the activity of these cells may be regulated by the agonists of peroxisome proliferator-activated nuclear receptors (PPARs). This study investigated the effects of a seven-day treatment with the PPAR β/δ agonist GW0742 (Fitorine, 5 mg/kg/day) on the behavior and gene expression of the astroglial and microglial proteins involved in the regulation of epileptogenesis in the rat brain within a lithium–pilocarpine model of temporal lobe epilepsy (TLE). TLE resulted in decreased social and increased locomotor activity in the rats, increased expression of astro- and microglial activation marker genes (Gfap, Aif1), pro- and anti-inflammatory cytokine genes (Tnfa, Il1b, Il1rn), and altered expression of other microglial (Nlrp3, Arg1) and astroglial (Lcn2, S100a10) genes in the dorsal hippocampus and cerebral cortex. GW0742 attenuated, but did not completely block, some of these impairments. Specifically, the treatment affected Gfap gene expression in the dorsal hippocampus and Aif1 gene expression in the cortex. The GW0742 injections attenuated the TLE-specific enhancement of Nlrp3 and Il1rn gene expression in the cortex. These results suggest that GW0742 may affect the expression of some genes involved in the regulation of epileptogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Phase-Dependent Response to Electrical Stimulation of Cortical Networks during Recurrent Epileptiform Short Discharge Generation In Vitro.

Author

Chizhov, Anton V., Tiselko, Vasilii S., Postnikova, Tatyana Yu., and Zaitsev, Aleksey V.

Subjects
EPILEPTIFORM discharges, ELECTRIC stimulation, LABORATORY rats, MATHEMATICAL models, HIPPOCAMPUS (Brain)
Abstract

The closed-loop control of pathological brain activity is a challenging task. In this study, we investigated the sensitivity of continuous epileptiform short discharge generation to electrical stimulation applied at different phases between the discharges using an in vitro 4-AP-based model of epilepsy in rat hippocampal slices. As a measure of stimulation effectiveness, we introduced a sensitivity function, which we then measured in experiments and analyzed with different biophysical and abstract mathematical models, namely, (i) the two-order subsystem of our previous Epileptor-2 model, describing short discharge generation governed by synaptic resource dynamics; (ii) a similar model governed by shunting conductance dynamics (Epileptor-2B); (iii) the stochastic leaky integrate-and-fire (LIF)-like model applied for the network; (iv) the LIF model with potassium M-channels (LIF+KM), belonging to Class II of excitability; and (v) the Epileptor-2B model with after-spike depolarization. A semi-analytic method was proposed for calculating the interspike interval (ISI) distribution and the sensitivity function in LIF and LIF+KM models, which provided parametric analysis. Sensitivity was found to increase with phase for all models except the last one. The Epileptor-2B model is favored over other models for subthreshold oscillations in the presence of large noise, based on the comparison of ISI statistics and sensitivity functions with experimental data. This study also emphasizes the stochastic nature of epileptiform discharge generation and the greater effectiveness of closed-loop stimulation in later phases of ISIs. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium–Pilocarpine Model of Epilepsy.

Author

Postnikova, Tatyana Y., Diespirov, Georgy P., Malkin, Sergey L., Chernyshev, Alexander S., Vylekzhanina, Elizaveta N., and Zaitsev, Aleksey V.

Subjects
ENTORHINAL cortex, PYRAMIDAL neurons, HIPPOCAMPUS (Brain), EPILEPSY, LABORATORY rats, DENDRITIC spines
Abstract

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium–pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unaltered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex terminates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant contributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Time- and Region-Specific Selection of Reference Genes in the Rat Brain in the Lithium–Pilocarpine Model of Acquired Temporal Lobe Epilepsy.

Author

Schwarz, Alexander P., Zakharova, Maria V., Kovalenko, Anna A., Dyomina, Alexandra V., Zubareva, Olga E., and Zaitsev, Aleksey V.

Subjects
TEMPORAL lobe epilepsy, GENE expression, LABORATORY rats, REVERSE transcriptase polymerase chain reaction, GENES
Abstract

Reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR) is a commonly used tool for gene expression analysis. The selection of stably expressed reference genes is required for accurate normalization. The aim of this study was to identify the optimal reference genes for RT-qPCR normalization in various brain regions of rats at different stages of the lithium–pilocarpine model of acquired epilepsy. We tested the expression stability of nine housekeeping genes commonly used as reference genes in brain research: Actb, Gapdh, B2m, Rpl13a, Sdha, Ppia, Hprt1, Pgk1, and Ywhaz. Based on four standard algorithms (geNorm, NormFinder, BestKeeper, and comparative delta-Ct), we found that after pilocarpine-induced status epilepticus, the stability of the tested reference genes varied significantly between brain regions and depended on time after epileptogenesis induction (3 and 7 days in the latent phase, and 2 months in the chronic phase of the model). Pgk1 and Ywhaz were the most stable, while Actb, Sdha, and B2m demonstrated the lowest stability in the analyzed brain areas. We revealed time- and region-specific changes in the mRNA expression of the housekeeping genes B2m, Actb, Sdha, Rpl13a, Gapdh, Hprt1, and Sdha. These changes were more pronounced in the hippocampal region during the latent phase of the model and are thought to be related to epileptogenesis. Thus, RT-qPCR analysis of mRNA expression in acquired epilepsy models requires careful selection of reference genes depending on the brain region and time of analysis. For the time course study of epileptogenesis in the rat lithium–pilocarpine model, we recommend the use of the Pgk1 and Ywhaz genes. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Study of the Composition and Properties of Bivalve Mollusk Shells as Promising Bio-Indifferent Materials for Photocatalytic Applications (Example of Practical Use).

Author

Zaitsev, Aleksey V. and Astapov, Ivan A.

Subjects
*BIVALVE shells, *SEASHELLS, *WATER purification, *BENDING strength, *CALCIUM carbonate, *BIVALVES, *BIOMASS liquefaction, *CLAMS
Abstract

This paper studies the composition and properties of shells of bivalve mollusks (Crenomytilus grayanus, Callista brevisiphonata, and Mizuhopecten yessoensis) from coastal discharges with a view to the possibility of their use in photocatalytic water treatment systems. The clam shells are considered in terms of application in the form of a powder material as a precursor for creating photocatalysts, and also as a carrier of photocatalytic coatings. It was shown that the main phase composing the shell material was calcium carbonate in two crystallographic modifications—calcite and aragonite. The presence of inorganic impurities in all studied clam shells did not exceed one mass percent. The main share was made up of elements included in the composition of calcium carbonate, which confirmed the high bio-indifference of the materials under study. Depending on the physiological and environmental features of the structure of clam shells, different contents of the organic component in their composition were observed. The granulometric characteristics of crushed clam shells (average diameter, specific surface area, and distribution modality) were studied. It was shown that the maximum values of bending strength of 5 MPa and compressive strength of 2 MPa are characterized by Mizuhopecten yessoensis shells with the lowest porosity of 2.91%. The features of sorption and photosorption processes of both whole and crushed shells in relation to four organic dyes at different temperatures and degrees of illumination were studied. Based on crushed shells of Mizuhopecten Yessoensis and titanium dioxide, functional materials (CaxTiyOz) were obtained, and their morphology and photocatalytic properties were studied. An example of the practical use of clam shells as a carrier of a photocatalytic coating is given. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Author

Zubareva, Olga E., primary, Dyomina, Alexandra V., additional, Kovalenko, Anna A., additional, Roginskaya, Anna I., additional, Melik-Kasumov, Tigran B., additional, Korneeva, Marina A., additional, Chuprina, Alesya V., additional, Zhabinskaya, Alesya A., additional, Kolyhan, Stepan A., additional, Zakharova, Maria V., additional, Gryaznova, Marusya O., additional, and Zaitsev, Aleksey V., additional

Published
2023
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15. Maternal Hyperhomocysteinemia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats

Author

Postnikova, Tatyana Y., primary, Amakhin, Dmitry V., additional, Trofimova, Alina M., additional, Tumanova, Natalia L., additional, Dubrovskaya, Nadezhda M., additional, Kalinina, Daria S., additional, Kovalenko, Anna A., additional, Shcherbitskaia, Anastasiia D., additional, Vasilev, Dmitry S., additional, and Zaitsev, Aleksey V., additional

Published
2022
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22. MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy

Author

Dyomina, Alexandra V., primary, Kovalenko, Anna A., additional, Zakharova, Maria V., additional, Postnikova, Tatiana Yu., additional, Griflyuk, Alexandra V., additional, Smolensky, Ilya V., additional, Antonova, Irina V., additional, and Zaitsev, Aleksey V., additional

Published
2022
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24. Maternal Hyperhomocysteinemia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats.

Author

Postnikova, Tatyana Y., Amakhin, Dmitry V., Trofimova, Alina M., Tumanova, Natalia L., Dubrovskaya, Nadezhda M., Kalinina, Daria S., Kovalenko, Anna A., Shcherbitskaia, Anastasiia D., Vasilev, Dmitry S., and Zaitsev, Aleksey V.

Subjects
NEUROPLASTICITY, MEMORY disorders, LONG-term potentiation, HYPERHOMOCYSTEINEMIA, CORD blood, GLUTAMATE receptors, GABA receptors
Abstract

Maternal hyperhomocysteinemia (HCY) is a common pregnancy complication caused by high levels of the homocysteine in maternal and fetal blood, which leads to the alterations of the cognitive functions, including learning and memory. In the present study, we investigated the mechanisms of these alterations in a rat model of maternal HCY. The behavioral tests confirmed the memory impairments in young and adult rats following the prenatal HCY exposure. Field potential recordings in hippocampal slices demonstrated that the long-term potentiation (LTP) was significantly reduced in HCY rats. The whole-cell patch-clamp recordings in hippocampal slices demonstrated that the magnitude of NMDA receptor-mediated currents did not change while their desensitization decreased in HCY rats. No significant alterations of glutamate receptor subunit expression except GluN1 were detected in the hippocampus of HCY rats using the quantitative real-time PCR and Western blot methods. The immunofluorescence microscopy revealed that the number of synaptopodin-positive spines is reduced, while the analysis of the ultrastructure of hippocampus using the electron microscopy revealed the indications of delayed hippocampal maturation in young HCY rats. Thus, the obtained results suggest that maternal HCY disturbs the maturation of hippocampus during the first month of life, which disrupts LTP formation and causes memory impairments. [ABSTRACT FROM AUTHOR]

Published
2023
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25. Optogenetic Low-Frequency Stimulation of Principal Neurons, but Not Parvalbumin-Positive Interneurons, Prevents Generation of Ictal Discharges in Rodent Entorhinal Cortex in an In Vitro 4-Aminopyridine Model.

Author

Proskurina, Elena Y., Chizhov, Anton V., and Zaitsev, Aleksey V.

Subjects
ENTORHINAL cortex, INTERNEURONS, NEURONS, ELECTRIC stimulation, CONCENTRATION gradient, RODENTS, TEMPORAL lobe epilepsy
Abstract

Low-frequency electrical stimulation is used to treat some drug-resistant forms of epilepsy. Despite the effectiveness of the method in suppressing seizures, there is a considerable risk of side effects. An optogenetic approach allows the targeting of specific populations of neurons, which can increase the effectiveness and safety of low-frequency stimulation. In our study, we tested the efficacy of the suppression of ictal activity in entorhinal cortex slices in a 4-aminopyridine model with three variants of low-frequency light stimulation (LFLS): (1) activation of excitatory and inhibitory neurons (on Thy1-ChR2-YFP mice), (2) activation of inhibitory interneurons only (on PV-Cre mice after virus injection with channelrhodopsin2 gene), and (3) hyperpolarization of excitatory neurons (on Wistar rats after virus injection with archaerhodopsin gene). Only in the first variant did simultaneous LFLS of excitatory and inhibitory neurons replace ictal activity with interictal activity. We suggest that LFLS caused changes in the concentration gradients of K+ and Na+ cations across the neuron membrane, which activated Na-K pumping. According to the mathematical modeling, the increase in Na-K pump activity in neurons induced by LFLS led to an antiepileptic effect. Thus, a less specific and generalized optogenetic effect on entorhinal cortex neurons was more effective in suppressing ictal activity in the 4-aminopyridine model. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Anakinra Reduces Epileptogenesis, Provides Neuroprotection, and Attenuates Behavioral Impairments in Rats in the Lithium–Pilocarpine Model of Epilepsy

Author

Dyomina, Alexandra V., primary, Zubareva, Olga E., additional, Smolensky, Ilya V., additional, Vasilev, Dmitry S., additional, Zakharova, Maria V., additional, Kovalenko, Anna A., additional, Schwarz, Alexander P., additional, Ischenko, Alexander M., additional, and Zaitsev, Aleksey V., additional

Published
2020
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44. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3

Author

Newton, Adam J. H., primary, Seidenstein, Alexandra H., additional, McDougal, Robert A., additional, Pérez-Cervera, Alberto, additional, Huguet, Gemma, additional, M-Seara, Tere, additional, Haimerl, Caroline, additional, Angulo-Garcia, David, additional, Torcini, Alessandro, additional, Cossart, Rosa, additional, Malvache, Arnaud, additional, Skiker, Kaoutar, additional, Maouene, Mounir, additional, Ragognetti, Gianmarco, additional, Lorusso, Letizia, additional, Viggiano, Andrea, additional, Marcelli, Angelo, additional, Senatore, Rosa, additional, Parziale, Antonio, additional, Stramaglia, S., additional, Pellicoro, M., additional, Angelini, L., additional, Amico, E., additional, Aerts, H., additional, Cortés, J., additional, Laureys, S., additional, Marinazzo, D., additional, Bassez, I., additional, Faes, L., additional, Almgren, Hannes, additional, Razi, Adeel, additional, Van de Steen, Frederik, additional, Krebs, Ruth, additional, Aerts, Hannelore, additional, Kanari, Lida, additional, Dlotko, Pawel, additional, Scolamiero, Martina, additional, Levi, Ran, additional, Shillcock, Julian, additional, de Kock, Christiaan P.J., additional, Hess, Kathryn, additional, Markram, Henry, additional, Ly, Cheng, additional, Marsat, Gary, additional, Gillespie, Tom, additional, Sandström, Malin, additional, Abrams, Mathew, additional, Grethe, Jeffrey S., additional, Martone, Maryann, additional, De Gernier, Robin, additional, Solinas, Sergio, additional, Rössert, Christian, additional, Haelterman, Marc, additional, Massar, Serge, additional, Pasquale, Valentina, additional, Pastore, Vito Paolo, additional, Martinoia, Sergio, additional, Massobrio, Paolo, additional, Capone, Cristiano, additional, Tort-Colet, Núria, additional, Sanchez-Vives, Maria V., additional, Mattia, Maurizio, additional, Almasi, Ali, additional, Cloherty, Shaun L., additional, Grayden, David B., additional, Wong, Yan T., additional, Ibbotson, Michael R., additional, Meffin, Hamish, additional, Prince, Luke Y., additional, Tsaneva-Atanasova, Krasimira, additional, Mellor, Jack R., additional, Mazzoni, Alberto, additional, Rosa, Manuela, additional, Carpaneto, Jacopo, additional, Romito, Luigi M., additional, Priori, Alberto, additional, Micera, Silvestro, additional, Migliore, Rosanna, additional, Lupascu, Carmen Alina, additional, Franchina, Francesco, additional, Bologna, Luca Leonardo, additional, Romani, Armando, additional, Saray, Sára, additional, Van Geit, Werner, additional, Káli, Szabolcs, additional, Thomson, Alex, additional, Mercer, Audrey, additional, Lange, Sigrun, additional, Falck, Joanne, additional, Muller, Eilif, additional, Schürmann, Felix, additional, Todorov, Dmitrii, additional, Capps, Robert, additional, Barnett, William, additional, Molkov, Yaroslav, additional, Devalle, Federico, additional, Pazó, Diego, additional, Montbrió, Ernest, additional, Mochol, Gabriela, additional, Azab, Habiba, additional, Hayden, Benjamin Y., additional, Moreno-Bote, Rubén, additional, Balasubramani, Pragathi Priyadharsini, additional, Chakravarthy, Srinivasa V., additional, Muddapu, Vignayanandam R., additional, Gheorghiu, Medorian D., additional, Mimica, Bartul, additional, Withlock, Jonathan, additional, Mureșan, Raul C., additional, Zick, Jennifer L., additional, Schultz, Kelsey, additional, Blackman, Rachael K., additional, Chafee, Matthew V., additional, Netoff, Theoden I., additional, Roberts, Nicholas, additional, Nagaraj, Vivek, additional, Lamperski, Andrew, additional, Grado, Logan L., additional, Johnson, Matthew D., additional, Darrow, David P., additional, Lonardoni, Davide, additional, Amin, Hayder, additional, Di Marco, Stefano, additional, Maccione, Alessandro, additional, Berdondini, Luca, additional, Nieus, Thierry, additional, Stimberg, Marcel, additional, Goodman, Dan F. M., additional, Nowotny, Thomas, additional, Koren, Veronika, additional, Dragoi, Valentin, additional, Obermayer, Klaus, additional, Castro, Samy, additional, Fernandez, Mariano, additional, El-Deredy, Wael, additional, Xu, Kesheng, additional, Maidana, Jean Paul, additional, Orio, Patricio, additional, Chen, Weiliang, additional, Hepburn, Iain, additional, Casalegno, Francesco, additional, Devresse, Adrien, additional, Ovcharenko, Aleksandr, additional, Pereira, Fernando, additional, Delalondre, Fabien, additional, De Schutter, Erik, additional, Bratby, Peter, additional, Gallimore, Andrew R., additional, Klingbeil, Guido, additional, Zamora, Criseida, additional, Zang, Yunliang, additional, Crotty, Patrick, additional, Palmerduca, Eric, additional, Antonietti, Alberto, additional, Casellato, Claudia, additional, Erö, Csaba, additional, D’Angelo, Egidio, additional, Gewaltig, Marc-Oliver, additional, Pedrocchi, Alessandra, additional, Bytschok, Ilja, additional, Dold, Dominik, additional, Schemmel, Johannes, additional, Meier, Karlheinz, additional, Petrovici, Mihai A., additional, Shen, Hui-An, additional, Surace, Simone Carlo, additional, Pfister, Jean-Pascal, additional, Lefebvre, Baptiste, additional, Marre, Olivier, additional, Yger, Pierre, additional, Papoutsi, Athanasia, additional, Park, Jiyoung, additional, Ash, Ryan, additional, Smirnakis, Stelios, additional, Poirazi, Panayiota, additional, Felix, Richard A., additional, Dimitrov, Alexander G., additional, Portfors, Christine, additional, Daun, Silvia, additional, Toth, Tibor I., additional, Jędrzejewska-Szmek, Joanna, additional, Kabbani, Nadine, additional, Blackwel, Kim T., additional, Moezzi, Bahar, additional, Schaworonkow, Natalie, additional, Plogmacher, Lukas, additional, Goldsworthy, Mitchell R., additional, Hordacre, Brenton, additional, McDonnell, Mark D., additional, Iannella, Nicolangelo, additional, Ridding, Michael C., additional, Triesch, Jochen, additional, Maex, Reinoud, additional, Safaryan, Karen, additional, Steuber, Volker, additional, Tang, Rongxiang, additional, Tang, Yi-Yuan, additional, Verveyko, Darya V., additional, Brazhe, Alexey R., additional, Verisokin, Andrey Yu, additional, Postnov, Dmitry E., additional, Günay, Cengiz, additional, Panuccio, Gabriella, additional, Giugliano, Michele, additional, Prinz, Astrid A., additional, Varona, Pablo, additional, Rabinovich, Mikhail I., additional, Denham, Jack, additional, Ranner, Thomas, additional, Cohen, Netta, additional, Reva, Maria, additional, Rebola, Nelson, additional, Kirizs, Tekla, additional, Nusser, Zoltan, additional, DiGregorio, David, additional, Mavritsaki, Eirini, additional, Rentzelas, Panos, additional, Ukani, Nikul H., additional, Tomkins, Adam, additional, Yeh, Chung-Heng, additional, Bruning, Wesley, additional, Fenichel, Allison L., additional, Zhou, Yiyin, additional, Huang, Yu-Chi, additional, Florescu, Dorian, additional, Ortiz, Carlos Luna, additional, Richmond, Paul, additional, Lo, Chung-Chuan, additional, Coca, Daniel, additional, Chiang, Ann-Shyn, additional, Lazar, Aurel A., additional, Creaser, Jennifer L., additional, Lin, Congping, additional, Ashwin, Peter, additional, Brown, Jonathan T., additional, Ridler, Thomas, additional, Levenstein, Daniel, additional, Watson, Brendon O., additional, Buzsáki, György, additional, Rinzel, John, additional, Curtu, Rodica, additional, Nguyen, Anh, additional, Assadzadeh, Sahand, additional, Robinson, Peter A., additional, Sanz-Leon, Paula, additional, Forlim, Caroline G., additional, de Almeida, Lírio O. B., additional, Pinto, Reynaldo D., additional, Rodríguez, Francisco B., additional, Lareo, Ángel, additional, Forlim, Caroline Garcia, additional, Montero, Aaron, additional, Mosqueiro, Thiago, additional, Huerta, Ramon, additional, Rodriguez, Francisco B., additional, Changoluisa, Vinicio, additional, Cordeiro, Vinícius L., additional, Ceballos, César C., additional, Kamiji, Nilton L., additional, Roque, Antonio C., additional, Lytton, William W., additional, Knox, Andrew, additional, Rosenthal, Joshua J. C., additional, Popovych, Svitlana, additional, Liu, Liqing, additional, Wang, Bin A., additional, Tóth, Tibor I., additional, Grefkes, Christian, additional, Fink, Gereon R., additional, Rosjat, Nils, additional, Perez-Trujillo, Abraham, additional, Espinal, Andres, additional, Sotelo-Figueroa, Marco A., additional, Cruz-Aceves, Ivan, additional, Rostro-Gonzalez, Horacio, additional, Zapotocky, Martin, additional, Hoskovcová, Martina, additional, Kopecká, Jana, additional, Ulmanová, Olga, additional, Růžička, Evžen, additional, Gärtner, Matthias, additional, Duvarci, Sevil, additional, Roeper, Jochen, additional, Schneider, Gaby, additional, Albert, Stefan, additional, Schmack, Katharina, additional, Remme, Michiel, additional, Schreiber, Susanne, additional, Migliore, Michele, additional, Lupascu, Carmen A., additional, Bologna, Luca L., additional, Antonel, Stefano M., additional, Courcol, Jean-Denis, additional, Çelikok, Sami Utku, additional, Navarro-López, Eva M., additional, Şengör, Neslihan Serap, additional, Elibol, Rahmi, additional, Sengor, Neslihan Serap, additional, Özdemir, Mustafa Yasir, additional, Li, Tianyi, additional, Arleo, Angelo, additional, Sheynikhovich, Denis, additional, Nakamura, Akihiro, additional, Shimono, Masanori, additional, Song, Youngjo, additional, Park, Sol, additional, Choi, Ilhwan, additional, Jeong, Jaeseung, additional, Shin, Hee-sup, additional, Sadeh, Sadra, additional, Gleeson, Padraig, additional, Angus Silver, R., additional, Chatzikalymniou, Alexandra Pierri, additional, Skinner, Frances K., additional, Sanchez-Rodriguez, Lazaro M., additional, Sotero, Roberto C., additional, Hertäg, Loreen, additional, Mackwood, Owen, additional, Sprekeler, Henning, additional, Puhlmann, Steffen, additional, Weber, Simon N., additional, Higgins, David, additional, Naumann, Laura B., additional, Iyer, Ramakrisnan, additional, Mihalas, Stefan, additional, Ticcinelli, Valentina, additional, Stankovski, Tomislav, additional, McClintock, Peter V. E., additional, Stefanovska, Aneta, additional, Janjić, Predrag, additional, Solev, Dimitar, additional, Seifert, Gerald, additional, Kocarev, Ljupčo, additional, Steinhäuser, Christian, additional, Salmasi, Mehrdad, additional, Glasauer, Stefan, additional, Stemmler, Martin, additional, Zhang, Danke, additional, Zhang, Chi, additional, Stepanyants, Armen, additional, Goncharenko, Julia, additional, Kros, Lieke, additional, Davey, Neil, additional, de Zeeuw, Chris, additional, Hoebeek, Freek, additional, Sinha, Ankur, additional, Adams, Roderick, additional, Schmuker, Michael, additional, Psarrou, Maria, additional, Schilstra, Maria, additional, Torben-Nielsen, Benjamin, additional, Metzner, Christoph, additional, Schweikard, Achim, additional, Mäki-Marttunen, Tuomo, additional, Zurowski, Bartosz, additional, Marinazzo, Daniele, additional, Faes, Luca, additional, Stramaglia, Sebastiano, additional, Jordan, Henry O. 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Published
2017
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45. Transient Switching of NMDA-Dependent Long-Term Synaptic Potentiation in CA3-CA1 Hippocampal Synapses to mGluR1-Dependent Potentiation After Pentylenetetrazole-Induced Acute Seizures in Young Rats.

Author

Postnikova, Tatyana Y., Trofimova, Alina M., Ergina, Julia L., Zubareva, Olga E., Kalemenev, Sergey V., and Zaitsev, Aleksey V.

Subjects
STATUS epilepticus, METHYL aspartate receptors, HIPPOCAMPUS (Brain), NEUROPLASTICITY, GLUTAMATE receptors
Abstract

The mechanisms of impairment in long-term potentiation after status epilepticus (SE) remain unclear. We investigated the properties of LTP induced by theta-burst stimulation in hippocampal slices of rats 3 h and 1, 3, and 7 days after SE. Seizures were induced in 3-week old rats by a single injection of pentylenetetrazole (PTZ). Only animals with generalized seizures lasting more than 30 min were included in the experiments. The results revealed that LTP was strongly attenuated in the CA1 hippocampal area after PTZ-induced SE as compared with that in control animals. Saturation of synaptic responses following epileptic activity does not explain weakening of LTP because neither the quantal size of the excitatory responses nor the slopes of the input-output curves for field excitatory postsynaptic potentials changed in the post-SE rats. After PTZ-induced SE, NMDA-dependent LTP was suppressed, and LTP transiently switched to the mGluR1-dependent form. This finding does not appear to have been reported previously in the literature. An antagonist of NMDA receptors, D-2-amino-5-phosphonovalerate, did not block LTP induction in 3-h and 1-day post-SE slices. An antagonist of mGluR1, FTIDS, completely prevented LTP in 1-day post-SE slices; whereas it did not affect LTP induction in control and post-SE slices at the other studied times. mGluR1-dependent LTP was postsynaptically expressed and did not require NMDA receptor activation. Recovery of NMDA-dependent LTP occurred 7 day after SE. Transient switching between NMDA-dependent LTP and mGluR1-dependent LTP could play a role in the pathogenesis of acquired epilepsy. [ABSTRACT FROM AUTHOR]

Published
2019
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46. 26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

Author

Newton, Adam J H, Seidenstein, Alexandra H, McDougal, Robert A, Cervera, Alberto, Huguet, Gemma, Seara, Tere, Haimerl, Caroline, Garcia, David, Torcini, Alessandro, Cossart, Rosa, Malvache, Arnaud, Skiker, Kaoutar, Maouene, Mounir, Ragognetti, Gianmarco, Lorusso, Letizia, Viggiano, Andrea, Marcelli, Angelo, Senatore, Rosa, Parziale, Antonio, Stramaglia, S., Pellicoro, M., Angelini, L., Amico, E., Aerts, H., Cortés, J., Laureys, S., Marinazzo, D., Bassez, I., Faes, L., Almgren, Hannes, Razi, Adeel, Steen, Frederik, Krebs, Ruth, Aerts, Hannelore, Kanari, Lida, Dlotko, Pawel, Scolamiero, Martina, Levi, Ran, Shillcock, Julian, Kock, Christiaan P, Hess, Kathryn, Markram, Henry, Ly, Cheng, Marsat, Gary, Gillespie, Tom, Sandström, Malin, Abrams, Mathew, Grethe, Jeffrey S, Martone, Maryann, Gernier, Robin, Solinas, Sergio, Rössert, Christian, Haelterman, Marc, Massar, Serge, Pasquale, Valentina, Pastore, Vito P, Martinoia, Sergio, Massobrio, Paolo, Capone, Cristiano, Colet, Núria, Vives, Maria V, Mattia, Maurizio, Almasi, Ali, Cloherty, Shaun L, Grayden, David B, Wong, Yan T, Ibbotson, Michael R, Meffin, Hamish, Prince, Luke Y, Atanasova, Krasimira, Mellor, Jack R, Mazzoni, Alberto, Rosa, Manuela, Carpaneto, Jacopo, Romito, Luigi M, Priori, Alberto, Micera, Silvestro, Migliore, Rosanna, Lupascu, Carmen A, Franchina, Francesco, Bologna, Luca L, Romani, Armando, Saray, Sára, Geit, Werner, Káli, Szabolcs, Thomson, Alex, Mercer, Audrey, Lange, Sigrun, Falck, Joanne, Muller, Eilif, Schürmann, Felix, Todorov, Dmitrii, Capps, Robert, Barnett, William, Molkov, Yaroslav, Devalle, Federico, Pazó, Diego, Montbrió, Ernest, Mochol, Gabriela, Azab, Habiba, Hayden, Benjamin Y, Bote, Rubén, Balasubramani, Pragathi P, Chakravarthy, Srinivasa V, Muddapu, Vignayanandam R, Gheorghiu, Medorian D, Mimica, Bartul, Withlock, Jonathan, Mureșan, Raul C, Zick, Jennifer L, Schultz, Kelsey, Blackman, Rachael K, Chafee, Matthew V, Netoff, Theoden I, Roberts, Nicholas, Nagaraj, Vivek, Lamperski, Andrew, Grado, Logan L, Johnson, Matthew D, Darrow, David P, Lonardoni, Davide, Amin, Hayder, Marco, Stefano, Maccione, Alessandro, Berdondini, Luca, Nieus, Thierry, Stimberg, Marcel, Goodman, Dan F M, Nowotny, Thomas, Koren, Veronika, Dragoi, Valentin, Obermayer, Klaus, Castro, Samy, Fernandez, Mariano, Deredy, Wael, Xu, Kesheng, Maidana, Jean P, Orio, Patricio, Chen, Weiliang, Hepburn, Iain, Casalegno, Francesco, Devresse, Adrien, Ovcharenko, Aleksandr, Pereira, Fernando, Delalondre, Fabien, Schutter, Erik, Bratby, Peter, Gallimore, Andrew R, Klingbeil, Guido, Zamora, Criseida, Zang, Yunliang, Crotty, Patrick, Palmerduca, Eric, Antonietti, Alberto, Casellato, Claudia, Erö, Csaba, Angelo, Egidio, Gewaltig, Marc-Oliver, Pedrocchi, Alessandra, Bytschok, Ilja, Dold, Dominik, Schemmel, Johannes, Meier, Karlheinz, Petrovici, Mihai A, Shen, Hui-An, Surace, Simone C, Pfister, Jean-Pascal, Lefebvre, Baptiste, Marre, Olivier, Yger, Pierre, Papoutsi, Athanasia, Park, Jiyoung, Ash, Ryan, Smirnakis, Stelios, Poirazi, Panayiota, Felix, Richard A, Dimitrov, Alexander G, Portfors, Christine, Daun, Silvia, Toth, Tibor I, Szmek, Joanna, Kabbani, Nadine, Blackwel, Kim T, Moezzi, Bahar, Schaworonkow, Natalie, Plogmacher, Lukas, Goldsworthy, Mitchell R, Hordacre, Brenton, McDonnell, Mark D, Iannella, Nicolangelo, Ridding, Michael C, Triesch, Jochen, Maex, Reinoud, Safaryan, Karen, Steuber, Volker, Tang, Rongxiang, Tang, Yi-Yuan, Verveyko, Darya V, Brazhe, Alexey R, Verisokin, Andrey Y, Postnov, Dmitry E, Günay, Cengiz, Panuccio, Gabriella, Giugliano, Michele, Prinz, Astrid A, Varona, Pablo, Rabinovich, Mikhail I, Denham, Jack, Ranner, Thomas, Cohen, Netta, Reva, Maria, Rebola, Nelson, Kirizs, Tekla, Nusser, Zoltan, DiGregorio, David, Mavritsaki, Eirini, Rentzelas, Panos, Ukani, Nikul H, Tomkins, Adam, Yeh, Chung-Heng, Bruning, Wesley, Fenichel, Allison L, Zhou, Yiyin, Huang, Yu-Chi, Florescu, Dorian, Ortiz, Carlos L, Richmond, Paul, Lo, Chung-Chuan, Coca, Daniel, Chiang, Ann-Shyn, Lazar, Aurel A, Creaser, Jennifer L, Lin, Congping, Ashwin, Peter, Brown, Jonathan T, Ridler, Thomas, Levenstein, Daniel, Watson, Brendon O, Buzsáki, György, Rinzel, John, Curtu, Rodica, Nguyen, Anh, Assadzadeh, Sahand, Robinson, Peter A, Leon, Paula, Forlim, Caroline G, Almeida, Lírio O B, Pinto, Reynaldo D, Rodríguez, Francisco B, Lareo, Ángel, Montero, Aaron, Mosqueiro, Thiago, Huerta, Ramon, Rodriguez, Francisco B, Changoluisa, Vinicio, Cordeiro, Vinícius L, Ceballos, César C, Kamiji, Nilton L, Roque, Antonio C, Lytton, William W, Knox, Andrew, Rosenthal, Joshua J C, Popovych, Svitlana, Liu, Liqing, Wang, Bin A, Tóth, Tibor I, Grefkes, Christian, Fink, Gereon R, Rosjat, Nils, Trujillo, Abraham, Espinal, Andres, Figueroa, Marco A, Aceves, Ivan, Gonzalez, Horacio, Zapotocky, Martin, Hoskovcová, Martina, Kopecká, Jana, Ulmanová, Olga, Růžička, Evžen, Gärtner, Matthias, Duvarci, Sevil, Roeper, Jochen, Schneider, Gaby, Albert, Stefan, Schmack, Katharina, Remme, Michiel, Schreiber, Susanne, Migliore, Michele, Antonel, Stefano M, Courcol, Jean-Denis, Çelikok, Sami U, López, Eva M, Şengör, Neslihan S, Elibol, Rahmi, Sengor, Neslihan S, Özdemir, Mustafa Y, Li, Tianyi, Arleo, Angelo, Sheynikhovich, Denis, Nakamura, Akihiro, Shimono, Masanori, Song, Youngjo, Park, Sol, Choi, Ilhwan, Jeong, Jaeseung, Shin, Hee-sup, Sadeh, Sadra, Gleeson, Padraig, Silver, R., Chatzikalymniou, Alexandra P, Skinner, Frances K, Rodriguez, Lazaro M, Sotero, Roberto C, Hertäg, Loreen, Mackwood, Owen, Sprekeler, Henning, Puhlmann, Steffen, Weber, Simon N, Higgins, David, Naumann, Laura B, Iyer, Ramakrisnan, Mihalas, Stefan, Ticcinelli, Valentina, Stankovski, Tomislav, McClintock, Peter V E, Stefanovska, Aneta, Janjić, Predrag, Solev, Dimitar, Seifert, Gerald, Kocarev, Ljupčo, Steinhäuser, Christian, Salmasi, Mehrdad, Glasauer, Stefan, Stemmler, Martin, Zhang, Danke, Zhang, Chi, Stepanyants, Armen, Goncharenko, Julia, Kros, Lieke, Davey, Neil, Zeeuw, Chris, Hoebeek, Freek, Sinha, Ankur, Adams, Roderick, Schmuker, Michael, Psarrou, Maria, Schilstra, Maria, Nielsen, Benjamin, Metzner, Christoph, Schweikard, Achim, Marttunen, Tuomo, Zurowski, Bartosz, Marinazzo, Daniele, Faes, Luca, Stramaglia, Sebastiano, Jordan, Henry O C, Stringer, Simon M, Dendek, Elżbieta, Suffczyński, Piotr, Tam, Nicoladie, Zouridakis, George, Pollonini, Luca, Asl, Mojtaba M, Valizadeh, Alireza, Tass, Peter A, Nold, Andreas, Fan, Wei, Konrad, Sara, Endle, Heiko, Vogt, Johannes, Tchumatchenko, Tatjana, Herpich, Juliane, Tetzlaff, Christian, Luboeinski, Jannik, Nachstedt, Timo, Ciba, Manuel, Bahmer, Andreas, Thielemann, Christiane, Kuebler, Eric S, Tauskela, Joseph S, Thivierge, Jean-Philippe, Bakker, Rembrandt, Amado, María, Evangelio, Marian, Clascá, Francisco, Tiesinga, Paul, Buckley, Christopher L, Toyoizumi, Taro, Dubreuil, Alexis M, Monasson, Rémi, Treves, Alessandro, Spalla, Davide, Rosay, Sophie, Kleberg, Florence I, Wong, Willy, Floriano, Bruno, Matsuo, Toshihiko, Uchida, Tetsuya, Dibenedetto, Domenica, Uludağ, Kâmil, Goodarzinick, Abdorreza, Schmidt, Maximilian, Hilgetag, Claus C, Diesmann, Markus, Albada, Sacha J, Fauth, Michael, Rossum, Mark, Sánchez, Manuel, Amaducci, Rodrigo, Muñiz, Carlos, Elices, Irene, Arroyo, David, Levi, Rafael, Cohen, Ben, Chow, Carson, Vattikuti, Shashaank, Bertolotti, Elena, Burioni, Raffaella, Volo, Matteo, Vezzani, Alessandro, Menzat, Bayar, Vogels, Tim P, Wagatsuma, Nobuhiko, Saha, Susmita, Kapoor, Reena, Kerr, Robert, Wagner, John, Molino, Luis C G, Yang, Guangyu R, Mejias, Jorge F, Wang, Xiao-Jing, Song, Hanbing, Goodliffe, Joseph, Luebke, Jennifer, Weaver, Christina M, Thomas, John, Sinha, Nishant, Shaju, Nikhita, Maszczyk, Tomasz, Jin, Jing, Cash, Sydney S, Dauwels, Justin, Westover, M., Karimian, Maryam, Moerel, Michelle, Weerd, Peter, Burwick, Thomas, Westra, Ronald L, Abeysuriya, Romesh, Hadida, Jonathan, Sotiropoulos, Stamatios, Jbabdi, Saad, Woolrich, Mark, Bensmail, Chama, Wrobel, Borys, Zhou, Xiaolong, Ji, Zilong, Liu, Xiao, Xia, Yan, Wu, Si, Wang, Xiao, Zhang, Mingsha, Ofer, Netanel, Shefi, Orit, Yaari, Gur, Carnevale, Ted, Majumdar, Amit, Sivagnanam, Subhashini, Yoshimoto, Kenneth, Smirnova, Elena Y, Amakhin, Dmitry V, Malkin, Sergey L, Zaitsev, Aleksey V, Chizhov, Anton V, Zaleshina, Margarita, Zaleshin, Alexander, Barranca, Victor J, Zhu, George, Skilling, Quinton M, Maruyama, Daniel, Ognjanovski, Nicolette, Aton, Sara J, Zochowski, Michal, Wu, Jiaxing, Aton, Sara, Rich, Scott, Booth, Victoria, Budak, Maral, Bernal, Salvador, Neymotin, Samuel A, Suter, Benjamin A, Shepherd, Gordon M G, Felton, Melvin A, Yu, Alfred B, Boothe, David L, Oie, Kelvin S, Franaszczuk, Piotr J, Shuvaev, Sergey A, Başerdem, Batuhan, Zador, Anthony, Koulakov, Alexei A, Madrona, Víctor J, Pereda, Ernesto, Mirasso, Claudio R, Canals, Santiago, Masoli, Stefano, Rongala, Udaya B, Spanne, Anton, Jorntell, Henrik, Oddo, Calogero M, Vartanov, Alexander V, Neklyudova, Anastasia K, Kozlovskiy, Stanislav A, Kiselnikov, Andrey A, Marakshina, Julia A, Teleńczuk, Maria, Teleńczuk, Bartosz, Destexhe, Alain, Kuokkanen, Paula T, Kraemer, Anna, McColgan, Thomas, Carr, Catherine E, Kempter, Richard, Newton, Adam J H, Seidenstein, Alexandra H, McDougal, Robert A, Cervera, Alberto, Huguet, Gemma, Seara, Tere, Haimerl, Caroline, Garcia, David, Torcini, Alessandro, Cossart, Rosa, Malvache, Arnaud, Skiker, Kaoutar, Maouene, Mounir, Ragognetti, Gianmarco, Lorusso, Letizia, Viggiano, Andrea, Marcelli, Angelo, Senatore, Rosa, Parziale, Antonio, Stramaglia, S., Pellicoro, M., Angelini, L., Amico, E., Aerts, H., Cortés, J., Laureys, S., Marinazzo, D., Bassez, I., Faes, L., Almgren, Hannes, Razi, Adeel, Steen, Frederik, Krebs, Ruth, Aerts, Hannelore, Kanari, Lida, Dlotko, Pawel, Scolamiero, Martina, Levi, Ran, Shillcock, Julian, Kock, Christiaan P, Hess, Kathryn, Markram, Henry, Ly, Cheng, Marsat, Gary, Gillespie, Tom, Sandström, Malin, Abrams, Mathew, Grethe, Jeffrey S, Martone, Maryann, Gernier, Robin, Solinas, Sergio, Rössert, Christian, Haelterman, Marc, Massar, Serge, Pasquale, Valentina, Pastore, Vito P, Martinoia, Sergio, Massobrio, Paolo, Capone, Cristiano, Colet, Núria, Vives, Maria V, Mattia, Maurizio, Almasi, Ali, Cloherty, Shaun L, Grayden, David B, Wong, Yan T, Ibbotson, Michael R, Meffin, Hamish, Prince, Luke Y, Atanasova, Krasimira, Mellor, Jack R, Mazzoni, Alberto, Rosa, Manuela, Carpaneto, Jacopo, Romito, Luigi M, Priori, Alberto, Micera, Silvestro, Migliore, Rosanna, Lupascu, Carmen A, Franchina, Francesco, Bologna, Luca L, Romani, Armando, Saray, Sára, Geit, Werner, Káli, Szabolcs, Thomson, Alex, Mercer, Audrey, Lange, Sigrun, Falck, Joanne, Muller, Eilif, Schürmann, Felix, Todorov, Dmitrii, Capps, Robert, Barnett, William, Molkov, Yaroslav, Devalle, Federico, Pazó, Diego, Montbrió, Ernest, Mochol, Gabriela, Azab, Habiba, Hayden, Benjamin Y, Bote, Rubén, Balasubramani, Pragathi P, Chakravarthy, Srinivasa V, Muddapu, Vignayanandam R, Gheorghiu, Medorian D, Mimica, Bartul, Withlock, Jonathan, Mureșan, 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Published
2017
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48. Astrocytic Atrophy Following <italic>Status Epilepticus</italic> Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus.

Author

Plata, Alex, Lebedeva, Albina, Denisov, Pavel, Nosova, Olga, Postnikova, Tatiana Y., Pimashkin, Alexey, Brazhe, Alexey, Zaitsev, Aleksey V., Rusakov, Dmitri A., and Semyanov, Alexey

Subjects
ASTROCYTES, EPILEPSY, NEUROPLASTICITY
Abstract

Epilepsy is a group of neurological disorders commonly associated with the neuronal malfunction leading to generation of seizures. Recent reports point to a possible contribution of astrocytes into this pathology. We used the lithium-pilocarpine model of status epilepticus (SE) in rats to monitor changes in astrocytes. Experiments were performed in acute hippocampal slices 2–4 weeks after SE induction. Nissl staining revealed significant neurodegeneration in the pyramidal cell layers of hippocampal CA1, CA3 areas, and the hilus, but not in the granular cell layer of the dentate gyrus. A significant increase in the density of astrocytes stained with an astrocyte-specific marker, sulforhodamine 101, was observed in CA1 stratum (str.) radiatum. Astrocytes in this area were also whole-cell loaded with a morphological tracer, Alexa Fluor 594, for two-photon excitation imaging. Sholl analyses showed no changes in the size of the astrocytic domain or in the number of primary astrocytic branches, but a significant reduction in the number of distal branches that are resolved with diffraction-limited light microscopy (and are thought to contain Ca2+ stores, such as mitochondria and endoplasmic reticulum). The atrophy of astrocytic branches correlated with the reduced size, but not overall frequency of Ca2+ events. The volume tissue fraction of nanoscopic (beyond the diffraction limit) astrocytic leaflets showed no difference between control and SE animals. The results of spatial entropy-complexity spectrum analysis were also consistent with changes in ratio of astrocytic branches vs. leaflets. In addition, we observed uncoupling of astrocytes through the gap-junctions, which was suggested as a mechanism for reduced K+ buffering. However, no significant difference in time-course of synaptically induced K+ currents in patch-clamped astrocytes argued against possible alterations in K+ clearance by astrocytes. The magnitude of long-term-potentiation (LTP) was reduced after SE. Exogenous D-serine, a co-agonist of NMDA receptors, has rescued the initial phase of LTP. This suggests that the reduced Ca2+-dependent release of D-serine by astrocytes impairs initiation of synaptic plasticity. However, it does not explain the failure of LTP maintenance which may be responsible for cognitive decline associated with epilepsy. [ABSTRACT FROM AUTHOR]

Published
2018
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