The Anti-Inflammatory Drug Aspirin Does Not Protect Against Chemotherapy-Induced Memory Impairment by Paclitaxel in Mice.

Aeson Chang,Erica K Sloan,Alexandra I Ziegler,Ni-Chun Chung,David M Shackleford,Adam J Lawther,Adam K Walker

doi:10.3389/fonc.2020.564965

Abstract

Inflammation has been proposed to play a causal role in chemobrain which—if true—would represent an opportunity to repurpose existing anti-inflammatory drugs for the prevention and treatment of chemobrain. Here, we show that the chemoagent paclitaxel induces memory impairment and anhedonia in mice within 24 h of treatment cessation, but inflammation is not present until 2 weeks after treatment. We find no evidence of brain inflammation as measured by cytokine analysis at any time point. Furthermore, treating with aspirin to block inflammation did not affect paclitaxel-induced memory impairment. These findings suggest that inflammation may not be responsible for memory impairment induced by paclitaxel. These results contrast with recent findings of a causal role for inflammation in cancer-induced memory deficits in mice that were prevented by treatment with oral aspirin, suggesting that cognitive impairment in cancer patients undergoing treatment may arise from multiple convergent mechanisms.

Highlights

Cognitive impairment and mood disturbance are widespread in cancer patients and survivors who have received chemotherapy
We have previously reported that the antiinflammatory drug aspirin prevents tumor-induced cognitive impairment in a mouse model of metastatic breast cancer [11], suggesting its potential to be given to patients prior to chemotherapy to reduce cognitive impairment induced by the cancer
Correlation analyses confirmed that peripheral cytokines were not associated with memory performance (Supplementary Table 1). These findings show that immediate deficits in memory and mood were independent of peripheral inflammation

Summary

Introduction

Cognitive impairment and mood disturbance are widespread in cancer patients and survivors who have received chemotherapy. A primary hypothesis proposed to account for sustained cognitive impairment and mood-related disorders is that chemotherapy drives peripheral inflammation that is propagated to the brain to induce neuroinflammation, Chemobrain and Neuroinflammation thereby driving changes in cognition and mood. This “inflammation hypothesis” has been supported by findings of cognitive and mood symptoms in cancer patients and survivors that correlate with increases in proinflammatory cytokines and neutrophil-to-lymphocyte ratios during and after chemotherapy [6, 8]. Given that numerous studies have identified an increase in proinflammatory cytokines in response to chemotherapy, it is not surprising that inflammation would be considered a candidate mechanism [17,18,19]

Results

Discussion

Conclusion