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

Abstract:

:Alzheimer's disease (AD) is the most common dementia worldwide and is characterized by the presence of senile plaques by amyloid-beta (Aβ) 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 Aβ-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.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Calió ML,Mosini AC,Marinho DS,Salles GN,Massinhani FH,Ko GM,Porcionatto MA

doi

10.1016/j.nbd.2020.105219

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

105219

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(20)30494-0

journal_volume

148

pub_type

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