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Title 

Chronic treatment with combined chemotherapeutic agents affects hippocampal micromorphometry and function in mice, independently of neuroinflammation

Authors 

S KangS LeeJ KimJ C KimS H KimYeonghoon SonT ShinB YounJ S KimH WangM YangC Moon

Publisher 

Korean Society for Brain and Neural Science

Issue Date 

2018

Citation 

Experimental Neurobiology

Keywords 

ChemotherapyHippocampusNeurogenesisNeuroinflammationNeuronal architectureVasculature

Abstract 

Chemotherapeutic agents induce long-term side effects, including cognitive impairment and mood disorders, particularly in breast cancer survivors who have undergone chemotherapy. However, the precise mechanisms underpinning chemotherapy-induced hippocampal dysfunction remain unknown. In this study, we investigated the detrimental effects of chronic treatment with a combination of adriamycin and cyclophosphamide (AC) on the neuronal architecture and functions of the hippocampi of female C57BL/6 mice. After chronic AC administration, mice showed memory impairment (measured using a novel object recognition memory task) and depression-like behavior (measured using the tail suspension test and forced swim test). According to Golgi staining, chronic AC treatment significantly reduced the total dendritic length, ramification, and complexity as well as spine density and maturation in hippocampal neurons in a sub-region-specific manner. Additionally, the AC combination significantly reduced adult neurogenesis, the extent of the vascular network, and the levels of hippocampal angiogenesis-related factors. However, chronic AC treatment did not increase the levels of inflammation-related signals (microglial or astrocytic distribution, or the levels of pro-inflammatory cytokines or M1/M2 macrophage markers). Thus, chronic AC treatment changed the neuronal architecture of the adult hippocampus, possibly by reducing neurogenesis and the extent of the vasculature, independently of neuroinflammation. Such detrimental changes in micromorphometric parameters may explain the hippocampal dysfunction observed after cancer chemotherapy.

ISSN 

1226-2560

Link 

http://dx.doi.org/10.5607/en.2018.27.5.419

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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