In summary, we noted that aging rats markedly exhibited depression-like behavior after exposure to CUMS, with cognitive dysfunction, mature hippocampal neuron loss, and neurogenesis impairment, reduced the 5-MTHF content in the CSF and the hippocampus, altered CP polarity, and decreased levels of folate transport-related proteins, which confirmed that LOD does involve impaired folate brain transport and that CSF with a reduced 5- MTHF content might trigger the hippocampal neurological dysfunction. Here, CP is linked to depressive symptom measurement.