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

Molecular Neurobiology
Dong-Dong ShiZhang-Jin Zhang

Abstract

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-α (TNF-α) and in significant decreases in the levels of the anti-inflammatory cytokines IL-4 and I...Continue Reading

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Citations

Aug 27, 2019·Current Opinion in Oncology·Erin M Gibson, Michelle Monje
Apr 30, 2020·EMBO Molecular Medicine·Lien D Nguyen, Barbara E Ehrlich
Mar 7, 2021·Trends in Neurosciences·Erin M Gibson, Michelle Monje
Aug 8, 2021·International Journal of Molecular Sciences·Tiziana GenoveseRosanna Di Paola

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Methods Mentioned

BETA
transgenic
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

MEMRI
Ethovision
ImageJ

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