Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer's Disease Mouse Model: Role of Microglial and Neuroinflammation.

Abstract

MicrogliaarecloselylinkedtoAlzheimer'sdisease (AD) many yearsago; however, the pathological mechanisms of ADremainunclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice. In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia. We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatorymarkersinmicroglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice. In all leptin treatment group, the brain Aβ levels were decrease. We found increased levels of IL-1β, IL-6 and microglial activation in the hippocampus of adult mice. Usingagedmiceasan experimental model for chronicneuroinflammationand leptin resistance, the number of Iba-1+ microglia and the levels of IL-1β/IL-6 in the hippocampus were greatly increased as compared to the adult. But between the leptin treatment and un-treatment, there were no difference. Leptin signaling would regulate the activation of microglia and the release of inflammatory factors, but it is not the only underlying mechanism in the neuroprotective effects of AD pathogenesis.