Abstract
Autism spectrum disorder (ASD) is a developmental disability characterized by social deficits and repetitive stereotyped behaviors. There are currently no drugs available for the treatment of the core symptoms of ASD, suggesting an urgent need for new therapeutic strategies. The neurobiology of autism is complex, but emerging research indicates that defects in hippocampal neurogenesis are associated with ASD in both humans and mouse models of ASD, leading to the suggestion that restoring neurogenesis may be a novel therapeutic approach for ASD. Here, we found that postnatal treatment with TO901317 (TO), a potent liver X receptor (LXR) agonist, typically activated LXRβ and its target genes in the hippocampus, and alleviated the social deficits and stereotypical behaviors in BTBR T+ tf/J (BTBR) and valproic acid (VPA)-induced mouse models. In addition, we further confirmed that TO postnatal treatment also rescued the inhibition of adult hippocampal neurogenesis in these two models. In summary, our study suggests that LXR agonist targeting hippocampal neurogenesis may represent a novel potential therapy for ASD.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by impaired sociability, as well as restricted, repetitive patterns of interests and behaviors (Rubenstein and Merzenich, 2003; Currais et al, 2016; Chao et al, 2018)
After the intraperitoneal injection of TO, the relative mRNA level of LXRß in the hippocampus was markedly increased in the B6 and BTBR T+ tf/J (BTBR) mice compared with that in the same strains treated with saline (Figure 2B)
The relative mRNA level of LXRß in the hippocampus was upregulated in B6 and valproic acid (VPA)-exposed mice compared with that in mice treated with saline (Figure 2F)
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by impaired sociability, as well as restricted, repetitive patterns of interests and behaviors (Rubenstein and Merzenich, 2003; Currais et al, 2016; Chao et al, 2018). The incidence of ASD has increased dramatically, reaching 1 in 59 children (Baio et al, 2018). There is an urgent need to determine the etiology of ASD and search for an effective treatment. Despite a growing body of ASD studies, the mechanism underlying this disorder still remains poorly understood. No consensus has been reached regarding the neurobiological mechanisms of ASD, and many factors have been shown to be involved in the pathogenesis of ASD, such as synapse dysfunctions, neuroimmunity, oxidative stress, and neurogenesis (Pardo and Eberhart, 2007; Jyonouchi et al, 2008; Carpita et al, 2018)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
