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Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory
The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory rem...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842689/ https://www.ncbi.nlm.nih.gov/pubmed/29681766 http://dx.doi.org/10.1155/2018/3941840 |
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author | Li, Zhao Zhao, Shuang Zhang, Hai-Lin Liu, Peng Liu, Fei-Fei Guo, Yue-Xian Wang, Xiu-Li |
author_facet | Li, Zhao Zhao, Shuang Zhang, Hai-Lin Liu, Peng Liu, Fei-Fei Guo, Yue-Xian Wang, Xiu-Li |
author_sort | Li, Zhao |
collection | PubMed |
description | The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM) test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function. |
format | Online Article Text |
id | pubmed-5842689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-58426892018-04-21 Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory Li, Zhao Zhao, Shuang Zhang, Hai-Lin Liu, Peng Liu, Fei-Fei Guo, Yue-Xian Wang, Xiu-Li Mediators Inflamm Research Article The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM) test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function. Hindawi 2018-02-22 /pmc/articles/PMC5842689/ /pubmed/29681766 http://dx.doi.org/10.1155/2018/3941840 Text en Copyright © 2018 Zhao Li et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Zhao Zhao, Shuang Zhang, Hai-Lin Liu, Peng Liu, Fei-Fei Guo, Yue-Xian Wang, Xiu-Li Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory |
title | Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory |
title_full | Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory |
title_fullStr | Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory |
title_full_unstemmed | Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory |
title_short | Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory |
title_sort | proinflammatory factors mediate paclitaxel-induced impairment of learning and memory |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842689/ https://www.ncbi.nlm.nih.gov/pubmed/29681766 http://dx.doi.org/10.1155/2018/3941840 |
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