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

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

doi:10.3389/fonc.2020.564965

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

Front Oncol. 2020 Dec 14:10:564965. doi: 10.3389/fonc.2020.564965. eCollection 2020.

Authors

Aeson Chang¹, Ni-Chun Chung¹, Adam J Lawther², Alexandra I Ziegler¹, David M Shackleford³, Erica K Sloan^{1

4}, Adam K Walker^{1

2

4

5}

Affiliations

¹ Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
² Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW, Australia.
³ Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
⁴ Division of Cancer Surgery, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
⁵ School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.

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.

Keywords: anti-inflammatory drugs (NSAIDs); cancer; cognitive impairment; inflammation; memory.