Leptin induces proliferation of neuronal progenitors and neuroprotection in a mouse model of Alzheimer's disease
Version 2 2024-10-28, 04:04Version 2 2024-10-28, 04:04
Version 1 2023-05-17, 20:37Version 1 2023-05-17, 20:37
journal contribution
posted on 2024-10-28, 04:04authored byR Perez-Gonzalez, D Antequera, T Vargas, C Spuch, M Bolos, E Carro
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.
History
Publication title
Journal of Alzheimer's Disease
Volume
Suppl 2
Issue
s2
Pagination
17-25
ISSN
1387-2877
Department/School
Menzies Institute for Medical Research
Publisher
I O S Press
Publication status
Published
Place of publication
Netherlands
Socio-economic Objectives
280102 Expanding knowledge in the biological sciences