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

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 Aß levels were decrease. We found increased levels of IL-1ß, 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-1ß/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.

The Role of TDP-43 in Neurodegenerative Disease.

In recent years, more and more neurodegenerative diseases, such as ALS, FTLD and AD, have been found to share a common pathological feature, which is the depletion of TDP-43 in the nucleus and the accumulation of TDP-43 in the cytoplasm through hyperphosphorylation, ubiquitination and cleavage. Therefore, this kind of neurodegenerative disease is also called TDP-43 proteinopathy. This suggests that TDP-43 plays a role in the pathogenesis of disease. Current studies show that the pathophysiological mechanism of TDP-43 in neurodegeneration is very complex. In this review, we describe the structure of TDP-43, its main physiological functions, the possible pathogenesis and how TDP-43 provides a new pathway to treat neurodegenerative diseases.