Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory
| Autor: | Fei-Fei Liu, Xiuli Wang, Peng Liu, Yue-Xian Guo, Shuang Zhao, Hai-Lin Zhang, Zhao Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Side effect Paclitaxel Article Subject Immunology Interleukin-1beta Morris water navigation task Hippocampus Pharmacology Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Memory lcsh:Pathology Medicine Animals Learning Maze Learning TUNEL assay business.industry Tumor Necrosis Factor-alpha Cancer Cell Biology medicine.disease Rats Thalidomide chemistry 030220 oncology & carcinogenesis Tumor necrosis factor alpha business 030217 neurology & neurosurgery Research Article lcsh:RB1-214 |
| Zdroj: | Mediators of Inflammation, Vol 2018 (2018) Mediators of Inflammation |
| ISSN: | 1466-1861 0962-9351 |
| Popis: | 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-αand IL-1βin the hippocampus tissue. In addition, the TNF-αsynthesis 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-αis critically involved in the paclitaxel-induced impairment of learning and memory function. |
| Databáze: | OpenAIRE |
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