Chemotherapy-Induced Cognitive Impairment Is Associated with Cytokine Dysregulation and Disruptions in Neuroplasticity

被引:49
作者
Shi, Dong-Dong [1 ]
Huang, Yu-Hua [2 ]
Lai, Cora Sau Wan [2 ]
Dong, Celia M. [3 ]
Ho, Leon C. [3 ]
Wu, Ed X. [3 ]
Li, Qi [4 ]
Wang, Xiao-Min [5 ]
Chung, Sookja Kim [2 ]
Sham, Pak Chung [6 ]
Zhang, Zhang-Jin [1 ]
机构
[1] Univ Hong Kong, LKS Fac Med, Sch Chinese Med, Pokfulam, 10 Sassoon Rd, Hong Kong, Peoples R China
[2] Univ Hong Kong, LKS Fac Med, State Key Lab Pharmaceut Biotechnol, Sch Biomed Sci, Hong Kong, Peoples R China
[3] Univ Hong Kong, Dept Elect & Elect Engn, Lab Biomed Imaging & Signal Proc, Hong Kong, Peoples R China
[4] Univ Hong Kong, HKU SIRI, State Key Lab Cognit & Brain Sci, Dept Psychiat, Hong Kong, Peoples R China
[5] Univ Hong Kong, LKS Fac Med, Dept Anesthesiol, Hong Kong, Peoples R China
[6] Univ Hong Kong, Genome Res Ctr, State Key Lab Cognit & Brain Sci, Dept Psychiat, Hong Kong, Peoples R China
关键词
Chemotherapy; Cognitive impairment; Cytokines; Neuroplasticity; Manganese-enhanced magnetic resonance imaging (MEMRI); In vivo transcranial two-photon imaging; MEDIAL PREFRONTAL CORTEX; SPATIAL MEMORY; CHEMOBRAIN; MODEL;
D O I
10.1007/s12035-018-1224-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Chemotherapy-induced cognitive impairment, often referred to as chemobrain, is a common side effect. In this study, mice received three intraperitoneal injections of a combination of docetaxel, adriamycin, and cyclophosphamide (DAC) at 2-day intervals. A water maze test was used to examine cognitive performance, and manganese-enhanced magnetic resonance imaging (MEMRI) was used to examine hippocampal neuronal activity. The whole brain, prefrontal cortex, hippocampus, and blood samples were then collected for cytokine measurement. The DAC-treated mice displayed a significantly shorter duration spent in and fewer entries into the target quadrant of the water maze than the control mice and a pronounced decrease in MEMRI signal intensity in the hippocampal subregions. In a separate experiment using in vivo transcranial two-photon imaging, DAC markedly eliminated dendritic spines without changing the rate of spine formation, leading to a striking loss of spines in the medial prefrontal cortex. DAC treatment resulted in significant elevations in the levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor- (TNF-) and in significant decreases in the levels of the anti-inflammatory cytokines IL-4 and IL-10 in most of the sera and brain tissues examined. The IL-6 and TNF- levels of several sera and brain tissues showed strong inverse correlations with the duration and number of entries in the target quadrant of the water maze and with the hippocampal MEMRI signal intensity, but also showed striking positive correlations with spine elimination and loss. These results indicate that chemobrain is associated with cytokine dysregulation and disrupted neuroplasticity of the brain.
引用
收藏
页码:2234 / 2243
页数:10
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