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.
Lead-free piezoelectric ceramics like K 0.5 Na 0.5 NbO 3 (KNN) represent an emerging class of biomaterials for medical technology, as they can be used as components in implantable microelectromechanical systems (MEMS) and bioactive scaffolds for tissue stimulation. Such functional materials can act as working components in future in vivo devices, and their addition to current implant designs can greatly improve the biological interaction between host and implant. Despite this, only a few reports have studied the biocompatibility of these materials with living cells. In this work, we investigate the biological response of two different cell lines grown on KNN thin films, and we demonstrate excellent biocompatibility of the KNN films with the cells. Undoped and 0.5 mol % CaTiO 3 -doped KNN thin films with nanometer-sized roughness were deposited on platinized silicon (SiPt) substrates, and cell proliferation, viability, and morphology of human 161BR fibroblast cells and rat Schwann cells grown on the KNN films and SiPt substrates were investigated and compared to glass control samples. The results show that proliferation rates for the cells grown on the KNN thin films were equally high or higher than those on the glass control samples, and no cytotoxic effect from either the films or the substrate was observed. The work demonstrates that KNN thin films on SiPt substrates are very promising candidates for components in implantable medical devices.
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles. Interestingly, individuals with metabolic syndromes share some pathologies with those diagnosed with AD including neuroinflammation, insulin resistance and cognitive deficits. Leptin, an adipocyte-derived hormone, regulates metabolism, energy expenditure and satiety via its receptor, LepR. To investigate the possible involvement of leptin in AD, we examined the distribution of leptin and LepR in the brains of the 5XFAD mouse model of AD, utilizing immunofluorescent staining in young (10–12-weeks; n = 6) and old (48–52-weeks; n = 6) transgenic (Tg) mice, together with age-matched wild-type (WT) controls for both age groups (young-WT, n = 6; old-WT, n = 6). We also used double immunofluorescent staining to examine the distribution of leptin and leptin receptor expression in astrocytes. In young 5XFAD, young-WT and old-WT mice, we observed neuronal and endothelial expression of leptin and LepR throughout the brain. However, neuronal leptin and LepR expression in the old 5XFAD brain was significantly diminished. Reduced neuronal leptin and LepR expression was accompanied by plaque loading and neuroinflammation in the AD brain. A marked increase in astrocytic leptin and LepR was also observed in old 5XFAD mice compared to younger 5XFAD mice. We postulate that astrocytes may utilize LepR signalling to mediate and drive their metabolically active state when degrading amyloid in the AD brain. Overall, these findings provide evidence of impaired leptin and LepR signalling in the AD brain, supporting clinical and epidemiological studies performed in AD patients.
Background Alzheimer’s Disease (AD) is a slow progressing neurodegenerative disease with various environmental and endogenous factors implicated in its development. Two such factors include downregulation of tropomyosin receptor kinase B (TrkB) and its ligand, brain derived neurotrophic factor (BDNF), which normally facilitate the function and survival of neurons. While the exact causes of AD are still unknown, studies have shown that interventions such as aerobic exercise may reduce the risk of its progression. Interestingly, BDNF and TrkB each have unique expression patterns in the presence Aβ plaques and tau tangles, the main pathologies of AD; these patterns further fluctuate across different exercise types, intensities, and durations. Method In the current study, we used the 5XFAD mouse model of AD (36 weeks of age) to investigate the nature of exercise‐induced neurotrophin alterations. We compared transgenic mice (Tg) and their wild‐type (WT) littermates following an exercise regimen consisting of a 60‐minute/day steady‐state treadmill exercise protocol for 3 weeks. We used immunofluorescent staining to examine the cortical expression of BDNF and TrkB across these groups. Result We found similar levels of TrkB expression in both exercised groups (WT and Tg) but significantly lower TrkB expression in the exercised 5XFAD Tg mice compared to their sedentary littermates. We failed to observe changes in BDNF expression across any of the groups. Conclusion The ability of exercise to restore TrkB protein levels in 5XFAD Tg mice to those of exercised wildtype littermates, suggests that TrkB may be considered a potential target for therapeutic intervention. We further postulate that exercise may have a restorative function on cognition and thus may be a prospective therapeutic avenue of treatment for AD and associated cognitive disorders.
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