Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus
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 ch...
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00215/full |
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| author | Alex Plata Albina Lebedeva Pavel Denisov Olga Nosova Tatiana Y. Postnikova Tatiana Y. Postnikova Alexey Pimashkin Alexey Brazhe Aleksey V. Zaitsev Aleksey V. Zaitsev Dmitri A. Rusakov Dmitri A. Rusakov Alexey Semyanov Alexey Semyanov Alexey Semyanov |
| author_facet | Alex Plata Albina Lebedeva Pavel Denisov Olga Nosova Tatiana Y. Postnikova Tatiana Y. Postnikova Alexey Pimashkin Alexey Brazhe Aleksey V. Zaitsev Aleksey V. Zaitsev Dmitri A. Rusakov Dmitri A. Rusakov Alexey Semyanov Alexey Semyanov Alexey Semyanov |
| author_sort | Alex Plata |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T02:52:23Z |
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| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-11T02:52:23Z |
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| spelling | doaj.art-5150cf41606f4a728351b8253fc9a1282022-12-22T01:23:16ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-06-011110.3389/fnmol.2018.00215369334Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat HippocampusAlex Plata0Albina Lebedeva1Pavel Denisov2Olga Nosova3Tatiana Y. Postnikova4Tatiana Y. Postnikova5Alexey Pimashkin6Alexey Brazhe7Aleksey V. Zaitsev8Aleksey V. Zaitsev9Dmitri A. Rusakov10Dmitri A. Rusakov11Alexey Semyanov12Alexey Semyanov13Alexey Semyanov14UNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaUNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaUNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaUNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, RussiaDepartment of Medical Physics, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, RussiaUNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaDepartment of Biophysics, Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, RussiaLaboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, RussiaInstitute of Experimental Medicine, Almazov National Medical Research Centre, St. Petersburg, RussiaUNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaUCL Institute of Neurology, University College London, London, United KingdomUNN Institute of Neuroscience, N. I. Lobachevsky State University of Nizhny Novgorod, University of Nizhny Novgorod, Nizhny Novgorod, RussiaDepartment of Molecular Neurobiology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, RussiaAll-Russian Research Institute of Medicinal and Aromatic Plants, Moscow, RussiaEpilepsy 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.https://www.frontiersin.org/article/10.3389/fnmol.2018.00215/fullastrocyte remodelingepilepsyD-serinecalciumplasticityspatial entropy |
| spellingShingle | Alex Plata Albina Lebedeva Pavel Denisov Olga Nosova Tatiana Y. Postnikova Tatiana Y. Postnikova Alexey Pimashkin Alexey Brazhe Aleksey V. Zaitsev Aleksey V. Zaitsev Dmitri A. Rusakov Dmitri A. Rusakov Alexey Semyanov Alexey Semyanov Alexey Semyanov Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus Frontiers in Molecular Neuroscience astrocyte remodeling epilepsy D-serine calcium plasticity spatial entropy |
| title | Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus |
| title_full | Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus |
| title_fullStr | Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus |
| title_full_unstemmed | Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus |
| title_short | Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus |
| title_sort | astrocytic atrophy following status epilepticus parallels reduced ca2 activity and impaired synaptic plasticity in the rat hippocampus |
| topic | astrocyte remodeling epilepsy D-serine calcium plasticity spatial entropy |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00215/full |
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