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.

Altered Brain Leptin and Leptin Receptor Expression in the 5XFAD Mouse Model of Alzheimer’s Disease

“…Amyloid deposition was observed to be greater in old-Tg mice ( Figure 3 i-p) compared to young-Tg mice ( Figure 3 a–h). We had previously reported that 48–52-week-old 5XFAD mice had an increased astrocytic expression of glial fibrillary acidic protein (GFAP) [ 31 ]. Similarly, we observed increased astrocytic GFAP expression in the old-Tg mice ( Figure 3 f–k) compared to young-Tg mice ( Figure 3 c, d).…”

“…Furthermore, to test the effects of Aβ on astrocytes, Allaman et al exposed cultured astrocytes to Aβ 25-35 and found increased glucose metabolism in the cells [54]. Addition of Aβ [25][26][27][28][29][30][31][32][33][34][35] peptides to co-cultures of neurons and astrocytes resulted in impaired neuronal viability. The effect on neurons was abrogated by pre-treatment with PI3K inhibitors, leading the authors to conclude that the deleterious effects were mediated via PI3K signalling [54].…”

“…The procedure for amyloid plaque-labelling with thioflavin-S (ThS) has been reported by our group previously [ 31 ]. Briefly, 0.015% ThS (in 50% ethanol w / v ) was added to each section following the final PBS wash in the immunofluorescent staining above.…”

“…Staining quantification: Protein quantification analyses was performed using ImageJ version 1.8.0_172 (ImageJ, National Institutes of Health, Bethesda, MD, USA) as previously described [ 31 ]. Briefly, to determine neuronal protein levels, ten random neuronal cells per brain section were outlined with the freehand tracer tool in ImageJ.…”

Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy

“…Recently Anishchal et al demonstrated that in aged 5XFAD mouse model of AD the pattern of AdipoRs was significantly perturbed. In fact, they have shown a significant decreased expression of both AdipoRs in neurons, as well as a decrease in endothelial cells of AdipoR1, but robust expression of AdipoR2 in activated astrocytes [ 91 ]. They suggest that astrocytes may utilize AdipoR2 signalling to fuel their activated state in the AD Brain [ 91 ].…”