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.