Resveratrol nanoparticles are neuroprotective in a model of Alzheimer's disease

• Published in: Acta ophthalmologica (Oxford, England) England), 2022-12, Vol.100 (S275), p.n/a
• Main Authors: Shamsher, Ehtesham, Guo, Li, Davis, Benjamin, Luong, Vy, Ravindran, Nivedita, Somavarapu, Satyanarayana, Cordeiro, Francesca
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Bioavailability; Brn-3 protein; Cobalt; Cobalt chloride; Dementia disorders; Excitotoxicity; Hypoxia; Nanoparticles; Neurodegenerative diseases; Neuroimaging; Neuroprotection; Neuroprotective agents; Rehydration; Resveratrol; Retina; Retinal ganglion cells; Tau protein
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2022.0176

Purpose: Alzheimer's disease (AD) is the major cause of dementia in the world with increasing evidences of the retina being affected. Since no cure exists, there is an urgent unmet need to find new treatments. Resveratrol, a natural polyphenol found in red wine, has been advocated as a potential neuroprotectant in this disease. However, resveratrol has a low solubility and bioavailability limiting its clinical translation. In this study, we assessed a novel formulation of resveratrol in vitro and in vivo in a triple transgenic Alzheimer's disease (3xTg‐AD) mouse model. Methods: Resveratrol nanoparticles (RNs) were formulated using a thin rehydration technique. They were assessed in vitro on R28 cells against glutamate excitotoxicity and cobalt chloride induced hypoxia. Next, 3xTg‐AD mice received intranasally either RNs (n = 7) or an equivalent vehicle (n = 6) 5 days a week for 3 months. After 3 months of treatment, animals were imaged using Detection of Apoptosing Retinal Cells (DARC). DARC count was defined as the number of fluorescent spots counted by a masked investigator. After sacrifice, their brains were harvested and immunostained for amyloid‐beta (Aβ) and phosphorylated tau (pTau). Retinas were immunostained with Brn3a, a retinal ganglion cell (RGC) marker. Results: RN formulation incorporating over 10 mg/ml resveratrol was stable over 90 days. RNs were able to protect R28 cells exposed to glutamate compared to the vehicle (IC50 25.1 ± 0.4 vs. 14.4 ± 1.0 mM, p  0.05). In vivo, DARC count was reduced with RN treatment compared to the vehicle (7.7 ± 2.1 vs. 49.1 ± 13.3, p  0.05). Interestingly, Aβ and pTau depositions in the brain were reduced compared to the vehicle (3.6 ± 0.2 vs. 4.5 ± 0.2 Aβ score, p