In the present study, it was found that continuous (10 days) leptin treatment counteracted the long-term increased sprouting of hippocampal mossy fibers and cognitive impairment, as well as corrected the abnormal expressions of related gene in the hippocampus, including mitochondria markers PHB, PINK1, DRP1, and its executive molecular Cathepsin E, zinc transporter 3,4 (ZnT3, ZnT4), ZIP7 and memory marker CaMK II α. This evidence concerns the gene CAMK2G and Cognitive impairment.