Resveratrol Differently Modulates Group I Metabotropic Glutamate Receptors Depending on Age in SAMP8 Mice

Abstract

Glutamate homeostasis is critical for neurotransmission as this excitatory neurotransmitter has a relevant role in cognition functions through ionotropic and metabotropic glutamate receptors in the central nervous system. During the last years, the role of the group I metabotropic glutamate receptors (mGluRs) in neurodegenerative diseases such as Alzheimer's disease has been intensely investigated. Resveratrol (RSV) is a natural polyphenolic compound that is thought to have neuroprotective properties for human health. However, little is known about the action of this compound on mGluR signaling. Therefore, the aim of this study was to investigate the possible modulation of group I mGluRs in SAMP8 mice five and seven months of age supplemented with RSV in the diet. Data reported herein show that RSV plays a different modulatory action on group I mGluRs: mGluR 5 is downregulated as age increases, independently of RSV presence, and mGluR 1 is upregulated or downregulated by RSV treatment depending on age (i.e., depending on mGluR 5 levels). In addition, a neuroprotective role can be inferred for RSV as lower glutamate levels, higher synapsin levels, and unchanged caspase-3 activity were detected after RSV treatment. In conclusion, our findings indicate that RSV treatment modifies the group I mGluR-mediated glutamatergic system in SAMP8 mice, which could contribute to the beneficial effects of this natural polyphenol.

Adenosine Metabolism in the Cerebral Cortex from Several Mice Models during Aging

“…An age-related reduction in glutamate levels in the whole brain of SAMP8 mice from five- to seven-month-old mice was previously reported by our group [ 64 ]. In the present work, covering a wider time frame (3, 6, and 12 months) and a limited region (cerebral cortex), glutamate levels in SAMR1 mice were similar at three and six months, but decreased at 12 months.…”

“…Adenosine signaling also interacts with many other neurotransmitter systems such as glutamatergic signaling [ 56 , 57 ], which is also modulated by aging and has a role in neurodegeneration [ 58 , 59 , 60 , 61 ]. The glutamatergic system has been found to be altered in the human brain in AD patients [ 62 , 63 ] and also in the whole brain of SAMP8 mice [ 64 ].…”

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

“…In the whole-brain from SAMP8 mice, we have reported an age-related downregulation and desensitization of the A 1 receptor whereas A 2A was found to be fully functional [29,38]. Also mGluR 5 significantly decreased with aging [30]. These previous data suggest SAMP8 mice as a suitable model for ARs and mGluRs related research on neurodegenerative diseases.…”

“…However, an in vivo study by PET revealed a downregulation of mGluR 5 caused by Aβ in the limbic system in the 5xFAD mouse model as compared to wild type [60]. We have recently described a significant age-associated decrease in mGluR 5 density in the whole-brain of SAMP8 mice [30]. Interestingly, in the present work, a significant and robust reduction in mGluR 5 density was also detected in blood serum and exosomal fraction from 5 to 7-month-old.…”

“…Resveratrol (RSV) has been considered as an anti-aging molecule with several beneficial properties for health ranging from cardio- [24], and neuroprotection [25] as well as an antitumoral [26,27] and immunoregulatory [28] action, among others. Recently, it has been described the modulatory effect of RSV on adenosinergic [29] and glutamatergic systems [30] in the brain of SAMP8 mice from 5 and 7 months of age.…”