Disruption of leptin signalling in a mouse model of Alzheimer's disease.
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.
['King|Anna|A|', 'Brain|Anna|A|', 'Hanson|Kelsey|K|', 'Dittmann|Justin|J|', 'Vickers|James|J|', 'Fernandez-Martos|Carmen|C|http://orcid.org/0000-0002-6387-4456']
D000544:Alzheimer Disease D016564:Amyloid beta-Protein Precursor D000818:Animals D004195:Disease Models, Animal D006624:Hippocampus D020738:Leptin D051379:Mice D008822:Mice, Transgenic D009474:Neurons D053764:Presenilin-1 D054411:Receptors, Leptin D015398:Signal Transduction
Leptin Alzheimer’s disease (AD) Amyloid-beta (Aβ) Cognitive decline Long leptin receptor (Ob-Rb)