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Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats
Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein sig...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974205/ https://www.ncbi.nlm.nih.gov/pubmed/29875624 http://dx.doi.org/10.3389/fnins.2018.00337 |
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author | Li, Weiwei Yu, Lingling Yan, Xiaodi Cai, Linlin Wan, Li Teng, Qinyu Li, Yonghua Wang, Yun Xu, Haitao |
author_facet | Li, Weiwei Yu, Lingling Yan, Xiaodi Cai, Linlin Wan, Li Teng, Qinyu Li, Yonghua Wang, Yun Xu, Haitao |
author_sort | Li, Weiwei |
collection | PubMed |
description | Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein signaling, which was proposed to contribute to memory retention impairment in rats. Here, we first demonstrated that propofol perfusion could inhibit forskolin induced LTP in the rat hippocampal CA1 slices. Propofol also reduced the level of cAMP, which could be reversed by non-selective PDE inhibitor IBMX. We further discovered that propofol could increase both PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region. Furthermore, pretreatment of rolipram, a PDE4 inhibitor, rescued propofol induced inhibition of CA1 LTP and the impairment of hippocampus-dependent memory formation in rats. Thus, our results suggest that reduced levels of cAMP by increasing PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region plays an important role in the propofol-induced amnesia. |
format | Online Article Text |
id | pubmed-5974205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59742052018-06-06 Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats Li, Weiwei Yu, Lingling Yan, Xiaodi Cai, Linlin Wan, Li Teng, Qinyu Li, Yonghua Wang, Yun Xu, Haitao Front Neurosci Neuroscience Propofol inhibits long-term potentiation (LTP) in the hippocampal CA1 region and impedes episodic memory formation. However, the molecular mechanisms involved in the effect of propofol are still poorly understood. It had been reported that propofol inhibited cAMP response element binding protein signaling, which was proposed to contribute to memory retention impairment in rats. Here, we first demonstrated that propofol perfusion could inhibit forskolin induced LTP in the rat hippocampal CA1 slices. Propofol also reduced the level of cAMP, which could be reversed by non-selective PDE inhibitor IBMX. We further discovered that propofol could increase both PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region. Furthermore, pretreatment of rolipram, a PDE4 inhibitor, rescued propofol induced inhibition of CA1 LTP and the impairment of hippocampus-dependent memory formation in rats. Thus, our results suggest that reduced levels of cAMP by increasing PDE4 activity and PDE4AX protein expressions in the hippocampal CA1 region plays an important role in the propofol-induced amnesia. Frontiers Media S.A. 2018-05-23 /pmc/articles/PMC5974205/ /pubmed/29875624 http://dx.doi.org/10.3389/fnins.2018.00337 Text en Copyright © 2018 Li, Yu, Yan, Cai, Wan, Teng, Li, Wang and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Li, Weiwei Yu, Lingling Yan, Xiaodi Cai, Linlin Wan, Li Teng, Qinyu Li, Yonghua Wang, Yun Xu, Haitao Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats |
title | Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats |
title_full | Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats |
title_fullStr | Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats |
title_full_unstemmed | Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats |
title_short | Reduced Cyclic Adenosine Monophosphate Level in Hippocampal CA1 Participates in Propofol Induced Amnesia in Rats |
title_sort | reduced cyclic adenosine monophosphate level in hippocampal ca1 participates in propofol induced amnesia in rats |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974205/ https://www.ncbi.nlm.nih.gov/pubmed/29875624 http://dx.doi.org/10.3389/fnins.2018.00337 |
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