Targeting A3 Adenosine Receptor (A3AR) Attenuates Paclitaxel-induced Cognitive Impairment

摘要: Abstract ID 20618Poster Board 400Paclitaxel, standard-of-care first-line chemotherapy for epithelial ovarian cancer and triple negative breast cancer, was shown to impair learning and memory functions in >50% of cancer survivors. Underpinning mechanisms of this major neurotoxicity are still mostly unknown, and there are no FDA-approved interventions. We developed a mouse model of paclitaxel-induced cognitive impairment whose cumulative dose is comparable to the total dose per cycle used in breast cancer patients. Paclitaxel-treated mice showed significant cognitive impairment in different hippocampal tests (T-maze, Novel Object Place Recognition test, NOPRT). Learning and memory functions were improved by co-administration of the selective A3 adenosine receptor (A3AR) agonist, MRS5980, without adversely affecting anxiety-like behavior and locomotor activity. Noteworthy, A3AR agonists possess …