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bioRxiv · 10.1101/567636

Leptin reduces pathology and increases adult neurogenesis in a transgenic mouse model of Alzheimer’s disease

Calio, M. L.·Salles, G. N.·Marinho, D. S.·Mosini, A. C. F.·Massinhani, F. H.·Ko, G. M.·Porcionatto, M. A.
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Abstract

Alzheimers disease (AD) is the most common dementia worldwide, and is characterized by the presence, in the brain tissue, of extracellular senile plaques formed by amyloid beta (A{beta}) peptide and intracellular neurofibrillary tangles of hyperphosphorylated Tau protein. These changes lead to progressive neuronal degeneration and dysfunction, resulting in severe brain atrophy and cognitive deficits. With the discovery that neurogenesis persists in the adult mammalian brain, including brain regions affected by AD, studies of the use of neural stem cells for treatment of neurodegenerative diseases in order to repair and/or prevent neuronal cell loss have increased. Here we show that leptin increases neurogenesis in the dentate gyrus of adult mice as well as in the subventricular zone both in wild type and AD transgenic mouse model. Chronic administration of leptin to young mice increased neural stem cell proliferation with significant effects on differentiation and survival of newborn cells. Expression of the long form of leptin receptor, LepRb, was detected in the neurogenic niches by reverse transcription-PCR and immunohistochemistry. Moreover, leptin modulated astrogliosis and the formation of senile plaques. Additionally, leptin led to attenuation of A{beta}-induced neurodegeneration and superoxide anion production as revealed by Fluoro-Jade B and dihydroethidium (DHE) staining. Our study contributes to the understanding of the effects of leptin in the brain that may lead to the development of new therapies to treat Alzheimers disease.

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Calio, M. L., Salles, G. N., Marinho, D. S., Mosini, A. C. F., Massinhani, F. H., Ko, G. M., Porcionatto, M. A.. 2019-03-21. Leptin reduces pathology and increases adult neurogenesis in a transgenic mouse model of Alzheimer’s disease. https://doi.org/10.1101/567636

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