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

World J Biol Psychiatry. 2026 Jun 5:1-11. doi: 10.1080/15622975.2026.2677901. Online ahead of print.

ABSTRACT

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.

PMID:42247219 | DOI:10.1080/15622975.2026.2677901