The study investigates the role of miR-199b-5p in breast cancer (BC) metastasis to the brain. MiR-199b-5p is highly expressed in extracellular vesicles (EVs) from BC cells with brain metastatic potential and is associated with brain metastasis in BC patients. The study shows that miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2, SLC38A2/SNAT2, and SLC16A7/MCT2) in astrocytes and neurons, respectively, to disrupt the neuron-astrocyte metabolic coupling. This disruption leads to the retention of glutamate, glutamine, and lactate, promoting cancer cell growth and brain metastasis. In vivo experiments in mouse models confirmed the role of miR-199b-5p in enhancing brain metastasis. The findings suggest a mechanism by which cancer cells reprogram neural metabolism to facilitate brain metastasis, providing potential therapeutic targets for preventing and treating brain metastases.The study investigates the role of miR-199b-5p in breast cancer (BC) metastasis to the brain. MiR-199b-5p is highly expressed in extracellular vesicles (EVs) from BC cells with brain metastatic potential and is associated with brain metastasis in BC patients. The study shows that miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2, SLC38A2/SNAT2, and SLC16A7/MCT2) in astrocytes and neurons, respectively, to disrupt the neuron-astrocyte metabolic coupling. This disruption leads to the retention of glutamate, glutamine, and lactate, promoting cancer cell growth and brain metastasis. In vivo experiments in mouse models confirmed the role of miR-199b-5p in enhancing brain metastasis. The findings suggest a mechanism by which cancer cells reprogram neural metabolism to facilitate brain metastasis, providing potential therapeutic targets for preventing and treating brain metastases.