Hippocampal neuroinflammation following combined exposure to cyclophosphamide and naproxen in ovariectomized mice. (1st February 2023)

• Record Type: Journal Article
• Authors: Pavlock, Samantha; McCarthy, Deirdre M.; Kesarwani, Anisha; Jean-Pierre, Pascal; Bhide, Pradeep G.
• Is Part Of: International journal of neuroscience. Volume 133:Number 2(2023)
• Page Start: 159
• Page End: 168
• Publication Date: 2023-02-01
• Subjects: Chemotherapy -- neuroinflammation -- cytokines -- behavioral assay -- ovariectomy; Nervous system -- Periodicals; 612.805
• DOI: 10.1080/00207454.2021.1896508
• Languages: English
• ISSNs: 0020-7454

Abstract

Abstract: Aim: Cancer patients undergoing chemotherapy report cognitive changes collectively termed "chemo brain." Neuroinflammation is among the factors believed to contribute to "chemo brain" suggesting a potential beneficial role for anti-inflammatory drugs in cancer patients undergoing chemotherapy. We investigated whether the non-steroidal anti-inflammatory drug naproxen influenced hippocampal inflammation in non-tumor bearing female mice receiving the chemotherapy drug cyclophosphamide (CP). Materials and methods: Intact and ovariectomized C57BL/6 mice were used to examine potential role of ovarian hormones on neuroinflammation. The mice were placed on naproxen (375 ppm) or control diet, and a week later CP (100 mg/kg; i.p.) was administered every 3 days for 2 weeks. We analyzed hippocampal inflammatory biomarkers, anxiety-like behavior, spatial working memory, exploratory behavior, spontaneous locomotor activity and depression-like behavior. Results: CP produced significant effects on anti-inflammatory but not pro-inflammatory biomarkers. However, CP and naproxen in combination produced significant effects on both pro- and anti- inflammatory biomarkers. Naproxen and ovariectomy individually produced significant effects on pro- and anti-inflammatory biomarkers as well. Working memory and depression-like behavior were not significantly influenced by CP, naproxen or ovariectomy individually although CP and ovariectomy produced significant interaction effects on depression-like behavior. Exploratory behavior and locomotor activity showed significant effects of CP, and interaction between CP and naproxen was significant for locomotor activity. Conclusions: Ovariectomy, naproxen and a combination of CP and naproxen upregulate hippocampal pro- and anti- inflammatory biomarkers. None of the factors individually produce significant behavioral changes that could be consistent with chemo brain, although CP and ovariectomy in combination produced significant effects on depression-like behavior, a co-morbidity of chemo brain.