Long-term administration of resveratrol at low doses improves neurocognitive performance as well as cerebral blood flow and modulates the inflammatory pathways in the brain

Philippe Garrigue (1, 2) , Lourdes Mounien (1) , Serge Champion (3) , Yassin Mouhajir (1) , Laurent Pechere (4) , Benjamin Guillet (2, 1) , Jean-Francois Landrier (1) , Eric Seree (1)

1 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
2 CERIMED - Centre Européen de Recherche en Imagerie médicale
3 IMBE - Institut méditerranéen de biodiversité et d'écologie marine et continentale
4 Laboratoire IVERY

There is an increasing prevalence of coincident cerebrovascular deficiency and cognitive dysfunction with aging. Increased oxidative stress as well as inflammation that occurs with aging are associated with the impairment of cerebral vascularization. Interestingly, Resveratrol (RSV), a natural phytoalexin, is known to be a strong antioxidant and possesses anti-inflammatory properties. Collectively, these observations strongly suggest that RSV could protect against cerebral vascularization defect and then improves the decline cognitive function associated with aging. In order to test this hypothesis, we investigated the effect of a long-term RSV treatment (1.25 mg/day for 5 months) on cognitive performances of animals that we have allowed to age normally. Then, we further analyzed the gene expression profile and the cerebral blood flow in the brain. By means of novel object recognition (NOR) test, we observed that RSV enhanced NOR performances of aged rats. In addition, RSV enhanced cerebral blood flow during NOR task in aged rats. Using microarrays experiments, we also showed that several pathways related to inflammation and oxidative stress (Eicosanoid signaling, MIF-mediated innate immunity, NF-kB signaling, TNFR2 signaling, IL6 signaling, Production of nitric oxide and ROS) were down-regulated in the brain of RSV treatments rats compared to control rats. In conclusion, these results support that a long-term treatment with RSV improves cognitive performance in the elderly male rat model. This effect is associated with an increase in cerebral blood flow and a decrease in the expression of several pro-inflammatory pathways in the brain

Mots clés: Resveratrol; Cerebral blood flow; Inflammation; Cognition

Domaines: Sciences du Vivant [q-bio]

Philippe Garrigue, Lourdes Mounien, Serge Champion, Yassin Mouhajir, Laurent Pechere, et al.. Long-term administration of resveratrol at low doses improves neurocognitive performance as well as cerebral blood flow and modulates the inflammatory pathways in the brain. Journal of Nutritional Biochemistry, 2021, 97, pp.108786. ⟨10.1016/j.jnutbio.2021.108786⟩. ⟨hal-03395123⟩