title: Leptin induces proliferation of neuronal progenitors and neuroprotection in a mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with senile amyloid-β (Aβ) plaques, neuronal death, and cognitive decline. Neurogenesis in the adult hippocampus, which is notably affected by progressive neurodegeneration and Aβ pathology, is implicated in learning and memory regulation. Human postmortem brains of AD patients and AβPP/PS1 double transgenic mice show increased neurodegeneration. Leptin, an adipose-derived hormone, promotes neurogenesis in the adult hippocampus, but the way in which this process occurs in the AD brain is still unknown. Thus, we sought to determine if leptin stimulated the proliferation of neuronal precursors in AβPP/PS1 mice. We estimated the number proliferating hippocampal cells after intracerebroventricular administration of a lentiviral vector encoding leptin. After 3 months of treatment with leptin we observed an increase in the number of BrdU-positive cells in the subgranular zone of the dentate gyrus, as shown by morphometric analysis. This increase resulted mainly from an increased proliferation of neuronal precursors. Additionally, leptin led to an attenuation of Aβ-induced neurodegeneration, as revealed by Fluoro-Jade staining. Our results suggest that in AβPP/PS1 mice, leptin exerts changes resembling acute neurotrophic and neuroprotective effects. These effects could serve as the basis for the design of future treatment strategies in AD.
authors.affiliation: Neuroscience Group, Research Institute Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Pérez-González
authors.forename: Desiree
authors.initials: D
authors.lastname: Antequera
authors.forename: Teo
authors.initials: T
authors.lastname: Vargas
authors.forename: Carlos
authors.initials: C
authors.lastname: Spuch
authors.forename: Marta
authors.initials: M
authors.lastname: Bolós
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007211:Indoles; D020738:Leptin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009930:Organic Chemicals; D053764:Presenilin-1 / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016564:Amyloid beta-Protein Precursor; D000089622:Doublecortin Domain Proteins; D005452:Fluoresceins; D007211:Indoles; D020738:Leptin; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D009930:Organic Chemicals; C508853:PSEN1 protein, human; D053764:Presenilin-1; C435731:fluoro jade; D049452:Green Fluorescent Proteins; C007293:DAPI