Combating of hippocampal neuroinflammatory response by folic acid: helpful prospective in autistic-like phenotype induced following maternal separation stress

Objectives Maternal separation (MS) stress consider as a risk factor for the development of autistic-like phenotype. Neuroinflammation is involved in the pathophysiology of autism. Neuroprotective effects have been shown for folic acid. The effects of folic acid on autistic-like phenotype in MS mice, focusing its probable effects on gene expression of Hmgb1, Nlrp3 and mTOR in the hippocampus evaluated.Methods MS mice orally received normal saline (10 mL/kg) or folic acid at doses of 5, 10, and 20 mg/kg for 14 days. Three-chamber sociability, shuttle box, and marble burying tests (MBT) were performed. Hippocampal expression of Hmgb1, Nlrp3 and mTOR genes was measured.Results Folic acid increased the sociability index (SI) and social preference index (SPI) in the three-chamber test (p < 0.001 for all doses), increased step-through latency in the shuttle box test (p < 0.01 for dose of 20 mg/kg) and reduced repetitive behaviours in the MBT (p < 0.05, p < 0.01 and p < 0.001 for doses of 5, 10 and 20 mg/kg, respectively). Folic acid decreased the gene expression of Hmgb1, Nlrp3 and mTOR (p < 0.001 for all doses).Conclusions Folic acid alleviated autistic-like behaviours in MS mice, probably through decrease in Hmgb1, Nlrp3 and mTOR mRNA gene expressions in the hippocampus.