Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats
Disrupted glutamate clearance in the synaptic cleft leads to synaptic dysfunction and neurological diseases. Decreased glutamate removal from the synaptic cleft is known to cause excitotoxicity. Data on the physiological effects of increased glutamate clearance are contradictory. This study investig...
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2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Tatyana Y. Postnikova Sergey L. Malkin Maria V. Zakharova Ilya V. Smolensky Olga E. Zubareva Aleksey V. Zaitsev |
| author_facet | Tatyana Y. Postnikova Sergey L. Malkin Maria V. Zakharova Ilya V. Smolensky Olga E. Zubareva Aleksey V. Zaitsev |
| author_sort | Tatyana Y. Postnikova |
| collection | DOAJ |
| description | Disrupted glutamate clearance in the synaptic cleft leads to synaptic dysfunction and neurological diseases. Decreased glutamate removal from the synaptic cleft is known to cause excitotoxicity. Data on the physiological effects of increased glutamate clearance are contradictory. This study investigated the consequences of ceftriaxone (CTX), an enhancer of glutamate transporter 1 expression, treatment on long-term synaptic potentiation (LTP) in the hippocampus of young rats. In this study, 5-day administration of CTX (200 mg/kg) significantly weakened LTP in CA3-CA1 synapses. As shown by electrophysiological recordings, LTP attenuation was associated with weakening of N-Methyl-D-aspartate receptor (NMDAR)-dependent signaling in synapses. However, PCR analysis did not show downregulation of NMDAR subunits or changes in the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. We assume that extracellular burst stimulation activates fewer synapses in CTX-treated animals because increased glutamate reuptake results in reduced spillover, and neighboring synapses do not participate in neurotransmission. Attenuation of LTP was not accompanied by noticeable behavioral changes in the CTX group, with no behavioral abnormalities observed in the open field test or Morris water maze test. Thus, our experiments show that increased glutamate clearance can impair long-term synaptic plasticity and that this phenomenon can be considered a potential side effect of CTX treatment. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:45:53Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6bcbe3ccc0ab428186860331366cd4002023-11-22T07:55:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216841710.3390/ijms22168417Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young RatsTatyana Y. Postnikova0Sergey L. Malkin1Maria V. Zakharova2Ilya V. Smolensky3Olga E. Zubareva4Aleksey V. Zaitsev5Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza Prospekt, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza Prospekt, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza Prospekt, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza Prospekt, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza Prospekt, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza Prospekt, 194223 Saint Petersburg, RussiaDisrupted glutamate clearance in the synaptic cleft leads to synaptic dysfunction and neurological diseases. Decreased glutamate removal from the synaptic cleft is known to cause excitotoxicity. Data on the physiological effects of increased glutamate clearance are contradictory. This study investigated the consequences of ceftriaxone (CTX), an enhancer of glutamate transporter 1 expression, treatment on long-term synaptic potentiation (LTP) in the hippocampus of young rats. In this study, 5-day administration of CTX (200 mg/kg) significantly weakened LTP in CA3-CA1 synapses. As shown by electrophysiological recordings, LTP attenuation was associated with weakening of N-Methyl-D-aspartate receptor (NMDAR)-dependent signaling in synapses. However, PCR analysis did not show downregulation of NMDAR subunits or changes in the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. We assume that extracellular burst stimulation activates fewer synapses in CTX-treated animals because increased glutamate reuptake results in reduced spillover, and neighboring synapses do not participate in neurotransmission. Attenuation of LTP was not accompanied by noticeable behavioral changes in the CTX group, with no behavioral abnormalities observed in the open field test or Morris water maze test. Thus, our experiments show that increased glutamate clearance can impair long-term synaptic plasticity and that this phenomenon can be considered a potential side effect of CTX treatment.https://www.mdpi.com/1422-0067/22/16/8417long-term potentiationNMDA receptorhippocampusEAAT2memory |
| spellingShingle | Tatyana Y. Postnikova Sergey L. Malkin Maria V. Zakharova Ilya V. Smolensky Olga E. Zubareva Aleksey V. Zaitsev Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats International Journal of Molecular Sciences long-term potentiation NMDA receptor hippocampus EAAT2 memory |
| title | Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats |
| title_full | Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats |
| title_fullStr | Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats |
| title_full_unstemmed | Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats |
| title_short | Ceftriaxone Treatment Weakens Long-Term Synaptic Potentiation in the Hippocampus of Young Rats |
| title_sort | ceftriaxone treatment weakens long term synaptic potentiation in the hippocampus of young rats |
| topic | long-term potentiation NMDA receptor hippocampus EAAT2 memory |
| url | https://www.mdpi.com/1422-0067/22/16/8417 |
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