Department of Inorganic, Organic and Biochemistry, Faculty of Chemical and Technological Sciences, School of Medicine of Ciudad Real, Regional Center of Biomedical Research (CRIB), University of Castilla- La Mancha (UCLM), 13071 Ciudad Real, Spain.
Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Neuroscience, University of Barcelona, 08028 Barcelona, Spain.
Cells. 2020 Jul 7;9(7):1628. doi: 10.3390/cells9071628.
Adenosine (ARs) and metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCRs) that are modulated in the brain of SAMP8 mice, an animal model of Alzheimer's disease (AD). In the present work, it is shown the presence of ARs and mGluRs in blood serum and derived exosomes from SAMP8 mice as well as its possible modulation by aging and resveratrol (RSV) consumption. In blood serum, adenosine A and A receptors remained unaltered from 5 to 7 months of age. However, an age-related decrease in adenosine level was observed, while 5'-Nucleotidase activity was not modulated. Regarding the glutamatergic system, it was observed a decrease in mGluR density and glutamate levels in older mice. In addition, dietary RSV supplementation caused an age-dependent modulation in both adenosinergic and glutamatergic systems. These GPCRs were also found in blood serum-derived exosomes, which might suggest that these receptors could be released into circulation via exosomes. Interestingly, changes elicited by age and RSV supplementation on mGluR density, and adenosine and glutamate levels were similar to that detected in whole-brain. Therefore, we might suggest that the quantification of these receptors, and their corresponding endogenous ligands, in blood serum could have predictive value for early diagnosis in combination with other distinctive hallmarks of AD.
腺苷（ARs）和代谢型谷氨酸受体（mGluRs）是 G 蛋白偶联受体（GPCRs），在阿尔茨海默病（AD）动物模型 SAMP8 小鼠的大脑中受到调节。在本工作中，显示了 SAMP8 小鼠血清和衍生的外泌体中存在 ARs 和 mGluRs，以及衰老和白藜芦醇（RSV）消耗对其可能的调节作用。在血清中，从 5 个月到 7 个月大，腺苷 A 和 A 受体保持不变。然而，观察到腺苷水平随年龄增长而下降，而 5'-核苷酸酶活性未受调节。关于谷氨酸能系统，观察到老年小鼠 mGluR 密度和谷氨酸水平降低。此外，饮食 RSV 补充引起两种腺苷能和谷氨酸能系统的年龄依赖性调节。这些 GPCR 也存在于血清衍生的外泌体中，这可能表明这些受体可以通过外泌体释放到循环中。有趣的是，由年龄和 RSV 补充引起的 mGluR 密度以及腺苷和谷氨酸水平的变化与在全脑中检测到的变化相似。因此，我们可以推测，在结合 AD 的其他独特特征的情况下，对这些受体及其相应的内源性配体在血清中的定量可能具有早期诊断的预测价值。
