Leptin enhances adult neurogenesis and reduces pathological features in a transgenic mouse model of Alzheimer's disease

Autor(es)

Calio, Michele Longoni ^{[1, 2]} ; Mosini, Amanda Cristina ^[2] ; Marinho, Darci Souza ^[3] ; Salles, Geisa Nogueira ^[4] ; Massinhani, Fernando Henrique ^[1] ; Ko, Gui Mi ^[5] ; Porcionatto, Marimelia Aparecida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Lab Neurobiol, Dept Biochem, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Lab Neurobiol, Dept Physiol, BR-04039032 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Lab Genet Control, Dept Ginecol, BR-04023062 Sao Paulo, SP - Brazil

^[4] Univ Vale Paraiba, Lab Biomed Nanotechnol, Inst Res & Dev, BR-12244000 Sao Jose Dos Campos, SP - Brazil

^[5] Univ Fed Sao Paulo, Inst Pharmacol & Mol Biol INFAR, BR-04044020 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neurobiology of Disease; v. 148, JAN 2021.
• Citações Web of Science: 1

Resumo

Alzheimer's disease (AD) is the most common dementia worldwide and is characterized by the presence of senile plaques by amyloid-beta (A beta) and 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 (NSCs) for the treatment of neurodegenerative diseases to repair or prevent neuronal cell loss have increased. Here we demonstrate that leptin administration increases the neurogenic process in the dentate gyrus of the hippocampus as well as in the subventricular zone of lateral ventricles of adult and aged mice. Chronic treatment with leptin increased NSCs proliferation with significant effects on proliferation and differentiation of newborn cells. The expression of the long form of the leptin receptor, LepRb, was detected in the neurogenic niches by reverse qPCR and immunohistochemistry. Moreover, leptin modulated astrogliosis, microglial cell number 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 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 Alzheimer's disease. (AU)

• Processo FAPESP: 15/19231-8 - Crosstalk entre as vias Wnt, SHH e Notch na aquisição de fenótipo de célula-tronco por astrócitos reativos
• Beneficiário: Marimélia Aparecida Porcionatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular