Changes in Gut, Microbiome, and Cognition after Doxorubicin, Cyclophosphamide, and Paclitaxel Chemotherapy Treatment

Chemotherapy induced cognitive impairment (CICI), or “chemobrain”, is defined as an impairment in memory, learning, executive function, and attention following chemotherapy treatment. In this study, 12-week-old female C57/BL6 mice were treated with 8 once weekly intraperitoneal injections (IP) of the following chemotherapeutic treatment groups: 1) Doxorubicin (Dox), Cyclophosphamide (CYP), and Paclitaxel (PTX) (AC-T) or 2) saline. At 30 days after the last AC-T or Saline injection, mice underwent the three-chamber sociability test to assess social behavior and social memory. AC-T treated mice spent equal time with both the novel and the stranger mouse, indicating a deficit in social memory. RNA sequencing showed changes in networks associated with neurogenesis, axonal guidance and neurotransmission. Whole brains were harvested and flash frozen in 2-methylbutane. Hippocampal samples were collected from coronal slices using a 0.2mm tissue punch and were sent to the RNA Sequencing Core for processing. There were 6 samples for each treatment group: AC-T and Saline. RNA was extracted from samples using the Zymo Quick-DNA/RNA miniprep Plus Kit (Cat # D7003). mRNA Library was constructed using the Illumina TruSeq Stranded mRNA Library Prep kit (Cat # 20020594). Samples were run on a 200-cycle NextSeq 2000 P2 flow cell. Dragen (v 4.3.6) was used for binary base call conversion and FastQC (v 0.11.9) was used for quality control. Quantification was done using Salmon (v 1.9.0). Fastq files were uploaded into Qiagen Ingenuity Pathway Analysis (IPA) via the RNA-Seq Analysis Portal (https://digitalinsights.qiagen.com/IPA).