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.

Keywords:

• Alzheimer’s disease
• leptin
• microglial
• neuroinflammation
• aged

Ethics Approval

Chengde Medical University Affiliated Hospital Ethics Committee (CYFYLL2019007).

Consent for Publication

All authors have given final approval of the version and agreed with the publication of this study here.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest for this work.

Additional information

Funding

This work was supported by grants from the Natural Science Foundation of Hebei Province (H2019406165).