Dataset Information

Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.

ABSTRACT: Metabolic syndromes share common pathologies with Alzheimer's disease (AD). Adiponectin, an adipocyte-derived protein, regulates energy metabolism via its receptors, AdipoR1 and AdipoR2. To investigate the distribution of adiponectin receptors (AdipoRs) in Alzheimer's, we examined their expression in the aged 5XFAD mouse model of AD. In age-matched wild-type mice, we observed neuronal expression of both ARs throughout the brain as well as endothelial expression of AdipoR1. The pattern of receptor expression in the aged 5XFAD brain was significantly perturbed. Here, we observed decreased neuronal expression of both ARs and decreased endothelial expression of AdipoR1, but robust expression of AdipoR2 in activated astrocytes. We also observed AdipoR2-expressing astrocytes in the dorsomedial hypothalamic and thalamic mediodorsal nuclei, suggesting the possibility that astrocytes utilise AdipoR2 signalling to fuel their activated state in the AD brain. These findings provide further evidence of a metabolic disturbance and demonstrate a potential shift in energy utilisation in the AD brain, supporting imaging studies performed in AD patients.

SUBMITTER: Pratap AA

PROVIDER: S-EPMC7407895 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.

Pratap Anishchal A AA Holsinger R M Damian RMD

Pharmaceuticals (Basel, Switzerland) 20200712 7

Metabolic syndromes share common pathologies with Alzheimer's disease (AD). Adiponectin, an adipocyte-derived protein, regulates energy metabolism via its receptors, AdipoR1 and AdipoR2. To investigate the distribution of adiponectin receptors (AdipoRs) in Alzheimer's, we examined their expression in the aged 5XFAD mouse model of AD. In age-matched wild-type mice, we observed neuronal expression of both ARs throughout the brain as well as endothelial expression of AdipoR1. The pattern of recepto ...[more]

PMID: 32664663

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Project description:There is an urgent need to improve the translational validity of Alzheimer's disease (AD) mouse models. Introducing genetic background diversity in AD mouse models has been proposed as a way to increase validity and enable the discovery of previously uncharacterized genetic contributions to AD susceptibility or resilience. However, the extent to which genetic background influences the mouse brain proteome and its perturbation in AD mouse models is unknown. In this study, we crossed the 5XFAD AD mouse model on a C57BL/6J (B6) inbred background with the DBA/2J (D2) inbred background and analyzed the effects of genetic background variation on the brain proteome in F1 progeny. Both genetic background and 5XFAD transgene insertion strongly affected protein variance in the hippocampus and cortex (n = 3,368 proteins). Protein co-expression network analysis identified 16 modules of highly co-expressed proteins common across the hippocampus and cortex in 5XFAD and non-transgenic mice. Among the modules strongly influenced by genetic background were those related to small molecule metabolism and ion transport. Modules strongly influenced by the 5XFAD transgene were related to lysosome/stress responses and neuronal synapse/signaling. The modules with the strongest relationship to human disease-neuronal synapse/signaling and lysosome/stress response-were not significantly influenced by genetic background. However, other modules in 5XFAD that were related to human disease, such as GABA synaptic signaling and mitochondrial membrane modules, were influenced by genetic background. Most disease-related modules were more strongly correlated with AD genotype in the hippocampus compared with the cortex. Our findings suggest that the genetic diversity introduced by crossing B6 and D2 inbred backgrounds influences proteomic changes related to disease in the 5XFAD model, and that proteomic analysis of other genetic backgrounds in transgenic and knock-in AD mouse models is warranted to capture the full range of molecular heterogeneity in genetically diverse models of AD.

Dataset Information

Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.

Publications

Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer's Disease.

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