Antioxidant Effect of Leptin on Neurogenic Niches in a Model of Alzheimer's Disease

Oxidative stress is implicated in the pathophysiology of a wide variety of neurodegenerative disorders and its role in neurogenesis is becoming increasingly acknowledged. It is known that the production of reactive oxygen species (ROS) is related to Alzheimeru0027s disease (AD) progression and to the formation of Aβ plaques and tau neurofibrillary tangles. It has been show that leptin, an adipose tissue-derived hormone, is capable of reducing the amount of extracellular amyloid beta, tau phosphorylation in neuronal cells and can modulate neurogenesis in the adult hippocampus, although the mechanisms involved in this process in the AD brain are still unknown. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models. It is speculated that a deficiency in leptin levels or function may contribute to systemic and CNS abnormalities leading to disease progression. Here, we sought to determine if leptin is able to decreases the superoxide production in subventricular zone and hippocampus of double transgenic APP/PS1 and wild type mice. After 7 days of intraperitoneal administration of leptin, we estimated the oxidative stress levels. There was a significant decrease in superoxide production in the subgranular zone of the dentate gyrus and in the subventricular zone, as shown by DHE staining. We also observed an increasement of neurogenesis in these areas by immunostaining analysis. Our results indicate that acute administration of leptin decrease oxidative stress and increase cell proliferation in two neurogenic niches in the brain of Alzheimer’s Diseases model. We propose that targeting oxidative stress provides a novel way to regulate adult neurogenesis and manage different brain diseases such as AD.