Pratap Anishchal A, Holsinger R M Damian
Laboratory of Molecular Neuroscience and Dementia, Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia.
Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.
Pharmaceuticals (Basel). 2020 Jul 12;13(7):150. doi: 10.3390/ph13070150.
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.
代谢综合征与阿尔茨海默病（AD）有着共同的病理特征。脂联素是一种由脂肪细胞分泌的蛋白质，通过其受体AdipoR1和AdipoR2调节能量代谢。为了研究脂联素受体（AdipoRs）在阿尔茨海默病中的分布，我们检测了它们在AD的5XFAD老年小鼠模型中的表达。在年龄匹配的野生型小鼠中，我们观察到两种受体在全脑的神经元中均有表达，且AdipoR1在内皮细胞中表达。5XFAD老年小鼠脑内受体的表达模式受到显著干扰。在此，我们观察到两种受体的神经元表达均减少，AdipoR1的内皮细胞表达也减少，但在活化的星形胶质细胞中AdipoR2表达强烈。我们还在背内侧下丘脑和丘脑背内侧核中观察到表达AdipoR2的星形胶质细胞，这表明星形胶质细胞可能利用AdipoR2信号来维持其在AD脑内的活化状态。这些发现为代谢紊乱提供了进一步的证据，并证明了AD脑内能量利用的潜在转变，支持了在AD患者中进行的影像学研究。
