LEPTIN INDUCES PROLIFERATION OF NEURAL PROGENITORS IN ADULT TRANSGENIC MOUSE CELLS

Alzheimer's disease (AD) is the most common dementia, characterized by the senile plaques of amyloid beta (Aβ) and neurofibrillary tangles of hyperphosphorylated Tau protein. Adipocyte-derived hormone leptin has been recently implicated in the control of neuronal plasticity and there is growing evidence that leptin is able to ameliorate AD, but the way in which this process occurs in the AD brain is still unknown. To explore whether modulation of adult neurogenesis may contribute to leptin control of neuronal plasticity, we used the neurosphere assay of neural stem cells derived from the adult subventricular zone (SVZ) of the double transgenic mouse APP/PS1 of different ages. After 48h administration of leptin, we estimated the number of proliferating and differentiated progenitors/neural stem cells in SVZ cultures of young and aged mice by immunohistochemistry. The expression of the long form leptin receptor, LepRb, was also assessed by qPCR. Here we show that leptin increases proliferation and differentiation of neuronal progenitors/neural stem cells from SVZ. The increase in expression of specific leptin receptor (LepRb) transcripts, as revealed by RT-PCR, is associated with leptin treatment. Furthermore, leptin triggered withdrawal of neural stem cells from the cell cycle as monitored by Ki67 labeling. Our results indicate that acute administration of leptin increase proliferation of neural progenitor cells of young and aged mice. We believe that the better understanding of the effects of leptin in the brain may lead to the early development of new therapies for treating Alzheimer's disease.