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

Abstract

Background Microglia are closely linked to Alzheimer’s disease (AD) many years ago; however, the pathological mechanisms of AD remain unclear. The purpose of this study was to determine whether leptin affected microglia in the hippocampus of young and aged male APP/PS1 mice. Objective In a transgenic model of AD, we investigated the association between intraperitoneal injection of leptin and microglia. Methods We intraperitoneal injection of leptin (1mg/kg) every day for one week and analyzed inflammatory markers in microglia in the hippocampus of adult (6 months) and aged (12 months) APP/PS1 mice. Results 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. Using aged mice as an experimental model for chronic neuroinflammation and 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. Conclusion 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.

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

“…It fosters neuronal growth, synaptic plasticity, and protects neurons from apoptotic triggers. Leptin resistance, induced by IR, impairs neuroprotection, affecting memory and learning, further contributing to the pathophysiology of AD[ 156 - 160 ]. Similarly, ghrelin, often known as the "hunger hormone," has been recognized for its roles beyond appetite stimulation, including the promotion of neuronal survival, enhancement of neurogenesis, and facilitation of synaptic plasticity.…”