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Disruption of leptin signalling in a mouse model of Alzheimer's disease

journal contribution
posted on 2023-05-19, 23:08 authored by Anna KingAnna King, Brain, A, Hanson, K, Dittmann, J, James VickersJames Vickers, Carmen Fernandez-MartosCarmen Fernandez-Martos
Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer's disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling; however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice. Immunohistochemical labelling demonstrated that leptin and Ob-Rb proteins were localised to neocortical and hippocampal neurons in APP/PS1 and wildtype (WT) mice. Neuronal leptin and Ob-Rb immunolabelling was more prominent in the neocortex of both groups at 9 month of age, while, at 18 months, labelling was reduced in the hippocampus of APP/PS1 mice relative to WT. Immunoblotting analysis demonstrated decreased hippocampal leptin levels, concomitantly with an increased Ob-Rb levels, in APP/PS1 mice compared with WT controls at 18 month of age. While no leptin mRNA was found in either of the groups analysed, Ob-Rb mRNA was significantly decreased in the hippocampus of APP/PS1 mice at both ages analysed. In addition, a significant decreased protein kinase B (Akt) activity concomitantly with an upregulation of suppressor of cytokine signaling-3 (SOCS3) and protein-tyrosine phosphatase 1B (PTP1B) transcripts was present. Thus, these results collectively indicate alterations of leptin signalling in the hippocampus of APP/PS1 mice, providing novel insights about the pathways that could link aberrant leptin signaling to the pathological changes of AD.

History

Publication title

Metabolic Brain Disease

Volume

33

Issue

4

Pagination

1097-1110

ISSN

0885-7490

Department/School

Wicking Dementia Research Education Centre

Publisher

Kluwer Academic/Plenum Publ

Place of publication

233 Spring St, New York, USA, Ny, 10013

Rights statement

Copyright Springer Science+Business Media, LLC, part of Springer Nature 2018

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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