Prolonged sevoflurane exposure causes abnormal synapse development and dysregulates beta-neurexin and neuroligins in the hippocampus in neonatal rats
Copyright © 2022 Elsevier B.V. All rights reserved..
BACKGROUND: The underlying molecular mechanisms of the excitatory/inhibitory (E/I) imbalance induced by sevoflurane exposure to neonates remain poorly understood. This study aimed to investigate the long-term effects of prolonged sevoflurane exposure to neonatal rats during the peak period of synaptogenesis on the changes of trans-synaptic neurexin-neuroligin interactions, synaptic ultrastructure in the hippocampus and cognition.
METHODS: A total of 30 rat pups at postnatal day (P) 7 was randomly divided into two groups: the control group (exposed to 30 % oxygen balanced with nitrogen) and the sevoflurane group (exposed to 2.5 % sevoflurane plus 30 % oxygen balanced with nitrogen) for 6 h. Neurocognitive behaviors were assessed with the Open field test at P23-25 and the Morris water maze test at P26-30. The expression of β-neurexin (β-NRX), N-methyl-d-aspartate receptor 2 subunit (NR2A and NR2B), neuroligin-1 (NLG-1), neuroligin-2 (NLG-2), postsynaptic density protein-95 (PSD-95), α1-subunit of the γ-aminobutyric acid A receptor (GABAAα1) and gephyrin in the hippocampus at P30 were measured by Western blot. The ultrastructure of synapses was examined under electron microscope.
RESULTS: Prolonged sevoflurane exposure at P7 resulted in cognitive deficiency in adolescence, as well as the downregulation of β-NRX, NR2A, NR2B, NLG-1, and PSD-95, and the upregulation of GABAAα1, NLG-2, and gephyrin in the hippocampal CA3 region. Sevoflurane anesthesia also increased the number of symmetric synapses in the hippocampus.
CONCLUSIONS: Prolonged sevoflurane exposure during the brain development leads to cognitive deficiency and disproportion of excitatory/inhibitory synapses which may be caused by dysregulated expression of synaptic adhesion molecules of β-NRX and neuroligins.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:312 |
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Enthalten in: |
Journal of affective disorders - 312(2022) vom: 01. Sept., Seite 22-29 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhang, Wenhua [VerfasserIn] |
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Links: |
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Themen: |
β-Neurexin |
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Anmerkungen: |
Date Completed 11.07.2022 Date Revised 25.07.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.jad.2022.05.115 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM342130579 |
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100 | 1 | |a Zhang, Wenhua |e verfasserin |4 aut | |
245 | 1 | 0 | |a Prolonged sevoflurane exposure causes abnormal synapse development and dysregulates beta-neurexin and neuroligins in the hippocampus in neonatal rats |
264 | 1 | |c 2022 | |
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500 | |a Date Revised 25.07.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
520 | |a BACKGROUND: The underlying molecular mechanisms of the excitatory/inhibitory (E/I) imbalance induced by sevoflurane exposure to neonates remain poorly understood. This study aimed to investigate the long-term effects of prolonged sevoflurane exposure to neonatal rats during the peak period of synaptogenesis on the changes of trans-synaptic neurexin-neuroligin interactions, synaptic ultrastructure in the hippocampus and cognition | ||
520 | |a METHODS: A total of 30 rat pups at postnatal day (P) 7 was randomly divided into two groups: the control group (exposed to 30 % oxygen balanced with nitrogen) and the sevoflurane group (exposed to 2.5 % sevoflurane plus 30 % oxygen balanced with nitrogen) for 6 h. Neurocognitive behaviors were assessed with the Open field test at P23-25 and the Morris water maze test at P26-30. The expression of β-neurexin (β-NRX), N-methyl-d-aspartate receptor 2 subunit (NR2A and NR2B), neuroligin-1 (NLG-1), neuroligin-2 (NLG-2), postsynaptic density protein-95 (PSD-95), α1-subunit of the γ-aminobutyric acid A receptor (GABAAα1) and gephyrin in the hippocampus at P30 were measured by Western blot. The ultrastructure of synapses was examined under electron microscope | ||
520 | |a RESULTS: Prolonged sevoflurane exposure at P7 resulted in cognitive deficiency in adolescence, as well as the downregulation of β-NRX, NR2A, NR2B, NLG-1, and PSD-95, and the upregulation of GABAAα1, NLG-2, and gephyrin in the hippocampal CA3 region. Sevoflurane anesthesia also increased the number of symmetric synapses in the hippocampus | ||
520 | |a CONCLUSIONS: Prolonged sevoflurane exposure during the brain development leads to cognitive deficiency and disproportion of excitatory/inhibitory synapses which may be caused by dysregulated expression of synaptic adhesion molecules of β-NRX and neuroligins | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Developing brain | |
650 | 4 | |a Neuroligins | |
650 | 4 | |a Neurotoxicity | |
650 | 4 | |a Sevoflurane | |
650 | 4 | |a β-Neurexin | |
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700 | 1 | |a Chen, Yanxin |e verfasserin |4 aut | |
700 | 1 | |a Qin, Jingwen |e verfasserin |4 aut | |
700 | 1 | |a Lu, Junming |e verfasserin |4 aut | |
700 | 1 | |a Fan, Yanting |e verfasserin |4 aut | |
700 | 1 | |a Shi, Ziwen |e verfasserin |4 aut | |
700 | 1 | |a Song, Xingrong |e verfasserin |4 aut | |
700 | 1 | |a Li, Chuanxiang |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Tianyun |e verfasserin |4 aut | |
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