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

King, A ORCID: 0000-0003-1792-0965, Brain, A, Hanson, K ORCID: 0000-0002-4230-1827, Dittmann, J, Vickers, JC ORCID: 0000-0001-5671-4879 and Fernandez-Martos, C ORCID: 0000-0002-6387-4456 2018 , 'Disruption of leptin signalling in a mouse model of Alzheimer's disease' , Metabolic Brain Disease, vol. 33, no. 4 , pp. 1097-1110 , doi: 10.1007/s11011-018-0203-9.

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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 Type: Article
Authors/Creators:King, A and Brain, A and Hanson, K and Dittmann, J and Vickers, JC and Fernandez-Martos, C
Keywords: Dementia, Leptin, Alzheimer's disease, APP/PS1 mouse
Journal or Publication Title: Metabolic Brain Disease
Publisher: Kluwer Academic/Plenum Publ
ISSN: 0885-7490
DOI / ID Number: 10.1007/s11011-018-0203-9
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Copyright Springer Science+Business Media, LLC, part of Springer Nature 2018

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