The Counter Effect of Exercise on Cisplatin-Induced Cognitive and Proliferation Impairments

Maha Elbeltagy; Ramzi A Al-Horani; Tala S Alsharaeh; Amro H Alkhatib; Ibrahim Alawaisheh; Ahmad A Abuhani; Ahmed Salman

doi:10.7759/cureus.52526

The Counter Effect of Exercise on Cisplatin-Induced Cognitive and Proliferation Impairments

Cureus. 2024 Jan 18;16(1):e52526. doi: 10.7759/cureus.52526. eCollection 2024 Jan.

Authors

Maha Elbeltagy^{1

2}, Ramzi A Al-Horani³, Tala S Alsharaeh⁴, Amro H Alkhatib⁴, Ibrahim Alawaisheh⁴, Ahmad A Abuhani⁴, Ahmed Salman^{1

2}

Affiliations

¹ Department of Anatomy and Histology, Faculty of Medicine, The University of Jordan, Amman, JOR.
² Department of Anatomy, Faculty of Medicine, Menoufia University, Shibin El Kom, EGY.
³ Department of Exercise Science, Yarmouk University, Irbid, JOR.
⁴ Department of General Medicine, University of Jordan Hospital, Amman, JOR.

Abstract

Background Cisplatin, a widely used chemotherapeutic agent, offers therapeutic benefits for cancer treatment but often leads to adverse effects on neurogenesis and oxidative stress, causing cognitive impairment. Concurrent physical activity has been proposed as a potential strategy to counteract these side effects. This study aimed to investigate the impact of physical exercise on cisplatin-induced cognitive impairment in a mouse model. Methods Adult male mice (n=45) were divided into three groups: control, cisplatin-treated (2.3 mg/kg), and exercise/cisplatin. Cisplatin was administered intraperitoneally over one month, while the exercise/cisplatin group underwent moderate-intensity exercise alongside cisplatin treatment. Spatial memory was evaluated using the novel object recognition (NOR) task, and hippocampal proliferation and oxidative stress were examined using Ki-67 and glutathione peroxidase (GPx) immunohistochemistry (IHC) staining, respectively. Statistical analyses were performed using the GraphPad Prism 4.0 software (GraphPad Software, San Diego, CA). Results The cisplatin-treated mice exhibited significantly lower preference index (PI) scores in the NOR task compared to the control (p<0.001) and exercise/cisplatin (p<0.001) groups. IHC staining revealed impaired hippocampal proliferation and increased oxidative stress in the cisplatin-treated group relative to the control and exercise/cisplatin groups. The introduction of a moderate-intensity exercise protocol appeared to mitigate the decline in hippocampal proliferation and oxidative damage induced by cisplatin. Additionally, cisplatin-treated mice experienced weight loss, while exercise attenuated this effect. Conclusion Cisplatin treatment resulted in decreased memory, hippocampal proliferation, and weight loss in mice. Concurrent moderate-intensity exercise seemed to alleviate these effects, suggesting a potential role for physical activity in ameliorating cisplatin-induced cognitive decline. This study underscores the importance of incorporating exercise as a complementary strategy to enhance cognitive outcomes in cancer patients undergoing cisplatin treatment.

Keywords: chemobrain; cisplatin; cognition; ki-67; neurogenesis.