Pentoxifylline, possibly by modulating expression of claudins in the hippocampus attenuates autistic-related behaviours in male mice subjected to maternal separation stress

Objectives Maternal separation (MS) stress is a risk factor for abnormal behaviors including autism-like behaviors. The blood brain barrier (BBB) dysfunction is involved in the pathophysiology of autism spectrum disorder (ASD). Pentoxifylline (PTX), a methylxanthine commonly used for peripheral vascular disease, has been shown that exerted neuroprotective effects. This study aims to examine the effects of PTX on autistic-like behaviors in MS mice, considering its possible effects on gene expression of claudins (CLDNs), as main molecules regulates BBB integrity.Methods Forty male mice were used. While control, unstressed, mice treated with normal saline, MS mice treated with normal saline or PTX at doses of 10, 20, and 30 mg/kg for 2 weeks via intraperitoneal injection. Three-chamber sociability, shuttle box, and marble burying tests were performed. Gene expression of Cldn -1, Cldn- 5 and Cldn- 12 was assessed in the hippocampus.Results PTX improved the sociability and social preference indexes, improved passive avoidance memory and decreased repetitive behaviors. PTX decreased Cldn- 5 while increased Cldn -1 and Cldn- 12 genes in the hippocampus.Conclusions PTX mitigated autism-like behaviors in MS mice, probably via regulating of mRNA expression of Cldn -1, Cldn -5 and Cldn- 12 in the hippocampus.