Estudios científicos
Resveratrol Modulates and Reverses the Age-Related Effect on Adenosine-Mediated Signalling in SAMP8 Mice
Abstract:
Resveratrol (RSV) is a natural compound present in berries, grapes and red wine that has shown some neuroprotective properties, but the mechanism by which RSV exhibits its protective role is not very well understood yet. Little is known about the effect of RSV on adenosinergic system, a system regulated in an age-dependent manner in SAMP8 mice, widely considered as an Alzheimer's model. Therefore, the aim of the present work was to assess whether RSV intake was able to modulate the adenosine-mediated signalling in SAMP8 mice. Data showed herein clearly demonstrate the ability of RSV to modulate adenosine receptor gene expression as well as transduction pathway mediated by receptors expressed on plasma membrane. Interestingly, this polyphenol was able to reverse the age-related loss of adenosine A1 receptors and its corresponding signalling pathway. Moreover, adenosine A2A receptors were not modulated by aging or RSV, but A2A-mediated signalling was completely desensitized after RSV treatment compared to untreated mice. Enzymes involved on adenosine metabolism, such as 5'-nucleotidase and adenosine deaminase, were found to be reduced after RSV treatment, but adenosine levels remained unchanged. Nevertheless, an age-related decrease on 5'-nucleotidase activity and adenosine and related metabolite levels was observed. In conclusion, our data show that RSV modulates adenosine-mediated signalling, strongly suggesting that the role of RSV via adenosine receptor signalling and its modulation of neurotransmission in neurodegenerative diseases should be considered as new therapeutic target for RSV neuroprotective effect.
Comentarios divulgativos:
El resveratrol es un compuesto bioactivo que está presente en alimentos de origen vegetal, como el vino tinto. Este compuesto se ha relacionado con propiedades neuroprotectoras, pero se desconoce su mecanismo de acción. En este estudio los autores evalúan si el consumo de resveratrol puede regular la expresión del gen codificante para el receptor de la adenosina en ratones SAMP8, un modelo de Alzhéimer, dependiente de la edad.
Los resultados de este estudio mostraron que el resveratrol puede modular la expresión del gen de la adenosina y regular la vía de transducción dependiente de los receptores de la membrana plasmática. El resveratrol se asociaba con una menor pérdida de receptores de adenosina A1, debido a la edad, y con una mayor conservación de la vía de señalización. Lo que no ocurría en el caso de los receptores de adenosina A2A, que se desensibilizaban. Se observó que enzimas implicadas en el metabolismo de la adenosina se reducían, aunque los niveles de adenosina permanecían constantes, a excepción de la disminución asociada a la edad. De modo que, el resveratrol parece modular la vía de señalización regulada por la adenosina, y este mecanismo podría estar relacionado con su efecto positivo frente a enfermedades neurodegenerativas, teniendo potencial terapéutico.
