Exosomal MYD88 isolated from 4T1 breast cancer cells using microfluidic chips promotes depressive-like behavior through neural remodeling in the mPFC.

Depression is one of the most prevalent mental health diseases, which is characterized by functional or structural changes of neurons. Cancer-induced depression (CID) can bring more serious medical burden. Exosomes have been implicated in cancer progression and depressive disorders; however, their specific role in CID remains unclear. To investigate the role of exosomes in CID, exosomes derived from 4T1 breast cancer cells were extracted using microfluidic chips-based isolation method. Behavioral assessments were performed to explore the effects of intranasal exosomal myeloid differentiation factor 88 (MYD88) on depressive-like behaviors in mice. Additionally, the effects of exosomal MYD88 on neuronal structure and function were researched by Golgi staining, sholl analysis and electrophysiological recordings. Exosomes from 4T1 breast cancer cells induced depressive-like symptoms and altered neuronal structure and function in the medial prefrontal cortex (mPFC) by upregulating MYD88 levels. Conversely, exosomes with reduced MYD88 content did not produce these depressive-like symptoms, suggesting a critical role for MYD88 in the observed effects. Exosomal MYD88 contributes to the development of breast cancer-induced depression. These findings highlight the potential of targeting exosomal pathways, particularly MYD88, as a therapeutic strategy for managing depression in cancer patients.