Adenosine and Metabotropic Glutamate Receptors Are Present in Blood Serum and Exosomes from SAMP8 Mice: Modulation by Aging and Resveratrol

Abstract

<jats:p>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 A1 and A2A 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 mGluR5 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 mGluR5 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.</jats:p>

Small extracellular vesicles in plasma reveal molecular effects of modified Mediterranean-ketogenic diet in participants with mild cognitive impairment

“…An earlier study has reported that plasma exosomes reflect a similar change in the expression of glutamate receptor with aging as in the brain tissue of transgenic mice. 48 Further, MMKD targeted the suggesting a restoration of glutamate-glutamate receptor signaling, which is critical for long-term potentiation. For example, we observed an increased expression of GRIN1, an obligatory subunit of NMDA type glutamate receptor, while observing a decrease in the GRIN2A and GRIN2B subunits of NMDA receptors and a decrease in AMPA subunit GRIA1.…”

Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

“…All these findings suggest that glutamate released by nociceptive neurons may also stimulate PAG and ACC microglial cells, causing the synthesis and release of CatS, a protease that will induce neuronal membrane fractalkine breakdown, generating soluble fractalkine, which, in turn, acts again on the fractalkine receptors of microglial cells, facilitating the synthesis and release of inflammatory mediators that favor neuropathic pain in these supraspinal structures. Hence, considering that polyphenols have been reported to modulate metabotropic glutamate activity in preclinical models 85 , 86 , it can be suggested that polyphenols contained in either GSE or CE may modulate glutamatergic synapses, leading to central sensitization process modulation. Concretely, since the ascending nerve pathway from the spinal cord to the supraspinal structures is a glutamatergic pathway, it would be expected that some of these polyphenols could modulate this glutamatergic neurotransmission of the ascending nociceptive pathway and thus the transmission of action potentials and the reactivation of glial cells.…”

Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice

“…Moreover, we have described that a high-fat diet (HFD) and RSV diet modulate adenosinergic signalling in SAMP8 mice by increasing adenosine A 2 receptors and 5 -NT activity [29]. Interestingly, we found evidence of the presence in serum and exosomes of adenosine A 1 , A 2A , and mGlu5 receptors, and a potential association between brain and serum receptors levels, which were modulated by aging and resveratrol [30] Therefore, the present work aimed to investigate whether cholesterol metabolism was altered by age and RSV supplementation in the brain and blood serum of SAMP8 mice-an animal model of aging and Alzheimer's disease-and their potential link with the amyloidogenic pathway of APP.…”

“…Moreover, we have described that a high-fat diet (HFD) and RSV diet modulate adenosinergic signalling in SAMP8 mice by increasing adenosine A 2 receptors and 5′-NT activity [ 29 ]. Interestingly, we found evidence of the presence in serum and exosomes of adenosine A 1 , A 2A , and mGlu5 receptors, and a potential association between brain and serum receptors levels, which were modulated by aging and resveratrol [ 30 ]…”