Resveratrol is a phytoalexin that occurs in
Resveratrol is a phytoalexin that occurs in relatively large amounts in peanut, berries, grapes, and red wine (Soleas et al., 2001). A recent study showed that resveratrol prevents social deficit in an animal model of autism, indicating its potential for possible therapeutic use in children with autism. Resveratrol is also used as a therapeutic agent for the prevention and amelioration of a wide range of pathologies including neurodegenerative diseases such as Alzheimer\'s and Parkinson\'s diseases (Jin et al., 2008, Ho et al., 2010). The immunomodulatory effects of resveratrol are well recognized for its ability to decrease pro and anti-inflammatory cytokines and increase T regulatory TPEN pathway (Wang et al., 2013). The effects of resveratrol could be attributed to its wide range of pharmacological properties including antioxidant, cardioprotective, anticarcinogenic, neuroprotective, and anti-aging (Albani et al., 2010). However, the effect of resveratrol has not been explored in immune system by assessing the involvement of chemokine receptors.
The BTBR T+tf J (BTBR) mice are useful animal models for autism studies because they show low levels of sociability compared with the C57BL/6J (B6) mice (McFarlane et al., 2008, Silverman et al., 2010). The BTBR mice are inbred strains that show robust well-replicated impairments in social interactions, with high levels of repetitive self-grooming and minimal vocalization in social settings. These behaviors are all similar to the core symptoms of autism (McFarlane et al., 2008, Silverman et al., 2010). Furthermore, BTBR mice exhibit a number of immune abnormalities that are also observed in children with autism (Li et al., 2009). Therefore, the BTBR strain of mice is presently a favorable model for understanding the mechanisms that might underlie the pathogenesis of autism. The BTBR model has become a gold standard for assessing the potential efficacy of drugs that could be clinically used to treat autism. Based on the abnormal immune dysfunction observed in autism, we sought to elucidate the role of chemokine receptors, which are associated with immune activation. In this study, we hypothesized that resveratrol can ameliorate the neuroimmune dysfunction by downregulating chemokine receptor expression in a BTBR autistic mouse model.
Materials and methods
Discussion Resveratrol has been shown to provide a neuroprotective effect in dopaminergic neurons (Zhang et al., 2010). Resveratrol prevents social deficits in animal models of autism (Bambini-Junior et al., 2014) and improves the hippocampal atrophy in chronic fatigue syndrome by enhancing neurogenesis (Moriya et al., 2011). The actions of resveratrol against neuroinflammation appear to activate microglia, resulting in the decrease of pro inflammatory factors through the modulation of signal transduction pathways (Zhang et al., 2010). Resveratrol is widely recognized as an anti-oxidant, anti-inflammatory, anti-cancer, cardio-protective, and neuroprotective compound (Leonard et al., 2003) and has been shown to inhibit the levels of proinflammatory mediators (Sha et al., 2008). Previously, our results showed that resveratrol effectively reduced the prominent repetitive behavior of the BTBR mice. We also explored the effects of resveratrol on Th1, Th2, Th17, and Treg cells-related transcription factors (Bakheet et al., 2016b). The efficacy of resveratrol in reducing the repetitive behavior and regulating signal transcription factors is a novel finding and indicates the potential therapeutic usefulness of resveratrol in autism. In the current study, we further explored the effects of resveratrol on chemokine receptors. The study of the influence of chemokine receptors expression is still limited in neurological disorders, particularly using the BTBR autistic mice model. The BTBR are an inbred strain of mice, which display social deficits, reduced ultrasonic vocalizations in social settings, and high levels of repetitive self-grooming (Blanchard et al., 2012). Learning and memory deficits have been reported for BTBR in fear conditioning, water maze reversal, discrimination flexibility, and probabilistic reversal learning tests (Rutz and Rothblat, 2012). Stereotypy and behavior rigidity are widely known as the core and defining features of autism (Boyd et al., 2012, Scattoni et al., 2008). Clarifying the mechanisms and pathways involved in neurodevelopmental disorders such as autism is essential to understanding not only their etiology but also to discovering early diagnostic markers and prophylactic therapies.