Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy
Status epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium–pilocarpine model of epilepsy in rats reproduc...
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2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Tatyana Y. Postnikova Georgy P. Diespirov Dmitry V. Amakhin Elizaveta N. Vylekzhanina Elena B. Soboleva Aleksey V. Zaitsev |
| author_facet | Tatyana Y. Postnikova Georgy P. Diespirov Dmitry V. Amakhin Elizaveta N. Vylekzhanina Elena B. Soboleva Aleksey V. Zaitsev |
| author_sort | Tatyana Y. Postnikova |
| collection | DOAJ |
| description | Status epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium–pilocarpine model of epilepsy in rats reproduces many features of human temporal lobe epilepsy. In this work, using the lithium–pilocarpine model in three-week-old rats, we examined the morphological and electrophysiological changes in the hippocampus within a week following pilocarpine-induced seizures. We found that almost a third of the neurons in the hippocampus and dentate gyrus died on the first day, but this was not accompanied by impaired synaptic plasticity at that time. A diminished long-term potentiation (LTP) was observed following three days, and the negative effect of SE on plasticity increased one week later, being accompanied by astrogliosis. The attenuation of LTP was caused by the weakening of N-methyl-D-aspartate receptor (NMDAR)-dependent signaling. NMDAR-current was more than two-fold weaker during high-frequency stimulation in the post-SE rats than in the control group. Application of glial transmitter D-serine, a coagonist of NMDARs, allows the enhancement of the NMDAR-dependent current and the restoration of LTP. These results suggest that the disorder of neuron–astrocyte interactions plays a critical role in the impairment of synaptic plasticity. |
| first_indexed | 2024-03-10T03:56:59Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:56:59Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d7e570e904a64f4282ea39ecdd92d8e92023-11-23T08:45:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241335510.3390/ijms222413355Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe EpilepsyTatyana Y. Postnikova0Georgy P. Diespirov1Dmitry V. Amakhin2Elizaveta N. Vylekzhanina3Elena B. Soboleva4Aleksey V. Zaitsev5Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, RussiaStatus epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium–pilocarpine model of epilepsy in rats reproduces many features of human temporal lobe epilepsy. In this work, using the lithium–pilocarpine model in three-week-old rats, we examined the morphological and electrophysiological changes in the hippocampus within a week following pilocarpine-induced seizures. We found that almost a third of the neurons in the hippocampus and dentate gyrus died on the first day, but this was not accompanied by impaired synaptic plasticity at that time. A diminished long-term potentiation (LTP) was observed following three days, and the negative effect of SE on plasticity increased one week later, being accompanied by astrogliosis. The attenuation of LTP was caused by the weakening of N-methyl-D-aspartate receptor (NMDAR)-dependent signaling. NMDAR-current was more than two-fold weaker during high-frequency stimulation in the post-SE rats than in the control group. Application of glial transmitter D-serine, a coagonist of NMDARs, allows the enhancement of the NMDAR-dependent current and the restoration of LTP. These results suggest that the disorder of neuron–astrocyte interactions plays a critical role in the impairment of synaptic plasticity.https://www.mdpi.com/1422-0067/22/24/13355astrocyteD-serinetemporal lobe epilepsyNMDAfield potentiallong-term potentiation |
| spellingShingle | Tatyana Y. Postnikova Georgy P. Diespirov Dmitry V. Amakhin Elizaveta N. Vylekzhanina Elena B. Soboleva Aleksey V. Zaitsev Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy International Journal of Molecular Sciences astrocyte D-serine temporal lobe epilepsy NMDA field potential long-term potentiation |
| title | Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy |
| title_full | Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy |
| title_fullStr | Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy |
| title_full_unstemmed | Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy |
| title_short | Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy |
| title_sort | impairments of long term synaptic plasticity in the hippocampus of young rats during the latent phase of the lithium pilocarpine model of temporal lobe epilepsy |
| topic | astrocyte D-serine temporal lobe epilepsy NMDA field potential long-term potentiation |
| url | https://www.mdpi.com/1422-0067/22/24/13355 |
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