Abstract 5869: Exploring chronic stress-induced hippocampal changes in murine ovarian cancer models and their relevance to depressive-like behaviors

Abstract Patients with ovarian cancer (OC) often experience depression, which can negatively impact their quality of life and overall prognosis. Our research group has demonstrated that chronic stress (CS) induces systemic inflammation, contributing to disease progression. Other studies have also highlighted its role in the development of depressive symptoms. Microglia are key regulators of brain inflammation and serve as a primary source of brain-derived neurotrophic factor (BDNF), which is crucial for maintaining synaptic plasticity, neuronal survival, and reducing symptoms of depression. However, the influence of CS and OC on the development of depressive symptoms in OC patients remains poorly understood. This study aims to investigate whether CS and OC can induce changes in the hippocampus (HPC) that may lead to depressive-like behavior in mice with OC. We hypothesize that CS will increase microglial infiltration and inflammatory markers, while reducing BDNF levels and neuronal activity in the HPC of mice with OC. To test our hypothesis, we inoculated 8- to 12-week-old C57BL/6 mice with ID8luc or IG10luc OC cells and subjected them to daily restraint stress for four weeks. Upon sacrifice, we collected and processed their brains for immunofluorescence analysis of BDNF, IBA1, and c-Fos. Our data suggest that CS accelerated tumor growth and led to increased microglial infiltration, decreased BDNF levels, and reduced neuronal activity in the HPC. These findings align with the BDNF hypothesis, which posits that a loss of BDNF in the HPC is directly involved in the development of depression. This study lays the groundwork for further research on how OC and CS can modulate brain activity and behavior. Citation Format: Luinet Lee Melendez-Rodriguez, Luis M. Rivera-Perez, Yadiel A. Rivera-Lopez, Melanie Ortiz-Leon, Jaydiel Casiano-Martinez, Alanis P. Torres-Rosado, Zuliann S. Galarza-Ruiz, Nemesis J. Torres-Rivera, Orlando I. Torres-Rodriguez, Guillermo N. Armaiz-Pena. Exploring chronic stress-induced hippocampal changes in murine ovarian cancer models and their relevance to depressive-like behaviors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5869.