Daily intranasal resveratrol-conjugated gold nanoparticles administration promotes neuroprotection and improves neurological outcome in the R6/2 mouse model of Huntington's disease

Pan-apoptosis and involvement of the inflammatory process are the hallmarks of Huntington's disease (HD). Inflammation currently represents one of the potential therapeutic targets for slowing and fighting the pathological phenotype of HD. The immunomodulatory properties of natural compounds, such as resveratrol, have been demonstrated in various disease models and human clinical trials. In the present study, we evaluated the neuroprotective and anti-inflammatory effects of the daily intranasal administration of resveratrol-conjugated gold nanoparticles in awake R6/2 mice, the genetic animal model of HD. Transgenic mice were treated daily with resveratrol-conjugated gold nanoparticles (0.1 mg/kg/day) starting from 5 weeks of age corresponding to the prodromal stage of the disease. After sacrifice, histological and immunofluorescence studies were performed. We found that resveratrol treated R6/2 mice survived longer and displayed a significant partial recovery of motor performance compared with R6/2 mice that received the nanoparticles with vehicle. Primary outcome measures such as striatal atrophy, neuronal intranuclear inclusions, and modulation of microglial reaction revealed a neuroprotective effect of resveratrol conjugated gold nanoparticles. Resveratrol provided a significant increase of neuroglobin, a neuroprotective globin, along with activated CREB and BDNF in the mice medium spiny neurons, accompanied by a down modulation of neuroinflammation, which, combined, might explain the beneficial effects observed in this model. Our findings showed that nanoparticles loaded with a specific compound which acts on the mutated protein intranuclear inclusions and inflammatory components may represent a valid therapeutic strategy in slowing down the symptoms of HD neurodegeneration.