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

Citation

King, A and Brain, A and Hanson, K and Dittmann, J and Vickers, J and Fernandez-Martos, C, Disruption of leptin signalling in a mouse model of Alzheimer's disease, Metabolic Brain Disease, 33, (4) pp. 1097-1110. ISSN 0885-7490 (2018) [Refereed Article]

Copyright Statement

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

DOI: doi:10.1007/s11011-018-0203-9

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:dementia, leptin, Alzheimer's disease, APP/PS1 mouse
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
UTAS Author:King, A (Professor Anna King)
UTAS Author:Brain, A (Ms Anna Brain)
UTAS Author:Hanson, K (Miss Kelsey Hanson)
UTAS Author:Dittmann, J (Mr Justin Dittmann)
UTAS Author:Vickers, J (Professor James Vickers)
UTAS Author:Fernandez-Martos, C (Dr Carmen Fernandez-Martos)
ID Code:129686
Year Published:2018
Web of Science® Times Cited:6
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2018-12-13
Last Modified:2019-04-01
Downloads:0

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