Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory

• Published in: Mediators of inflammation Vol. 2018; no. 2018; pp. 1 - 9
• Main Authors: Wang, Xiu-Li, Liu, Fei-Fei, Liu, Peng, Zhang, Hai-Lin, Zhao, Shuang, Li, Zhao, Guo, Yue-Xian
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Analysis; Animals; Apoptosis; Brain; Brain research; Cancer; Chemotherapy; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; IL-1β; Inflammation; Interleukin-1beta - metabolism; Interleukins; Learning - drug effects; Male; Maze Learning - drug effects; Memory - drug effects; Neurons; Paclitaxel; Paclitaxel - therapeutic use; Quality of life; Rats; Rats, Sprague-Dawley; Rodents; Spatial discrimination learning; Spatial memory; Thalidomide; Thalidomide - pharmacology; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2018/3941840

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.