Supplementation with selenium attenuates autism-like behaviors and improves oxidative stress, inflammation and related gene expression in an autism disease model.

Autism spectrum disorder (ASD) refers to a group of neurodevelopmental disorders. The etiology and pathological mechanisms of ASD are still unknown, and its prognosis is poor. This study investigated the effects of selenium (Se) supplementation on abnormal behavior and cognitive function in ASD model mice, as well as the potential action pathways. BTBR mice were randomly assigned to either a model group (BTBR group), a model selenium supplement group (BTBR+Se group), a normal control group (B6 group) or a normal selenium supplement group (B6+Se group). Sodium selenite, at a dosage of 1 mg/kg/day, was administered to the selenium supplementation groups by gavage. The mice in the BTBR group and the B6 group received the same amount of 0.9% saline by gavage. After 4 weeks of continuous intervention, the social functions and cognitive behaviors of the mice and the selenium concentration in hippocampal tissue were assessed. Hippocampal tissue structures were observed. Changes in neurotransmitter levels, oxidative stress and neuroinflammatory indicators were detected. SelP protein expression was significantly lower in hippocampal tissue from BTBR mice than in hippocampal tissue from B6 mice. The administration of sodium selenite in BTBR mice: (1) increased the expression of SelP; (2) attenuated spatial learning, memory impairment and improved social behaviors; (3) changed the serum levels of 5-HT, DA and Glu; (4) decreased the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α in serum and hippocampal tissue; (5) reduced the ROS and MDA contents and significantly increased SOD activity, CAT activity, GSH-px activity, and antioxidant GSH levels; and (6) protected against neuronal loss in the hippocampus. Se supplementation significantly improved the social functioning, repetitive stereotyped behavior and cognitive function in BTBR mice. Se may play a protective role in the hippocampus of BTBR mice by regulating neurotransmitter levels, reducing oxidative stress, alleviating neuroinflammation and rescuing neural cell damage.

Folic acid improves abnormal behavior via mitigation of oxidative stress, inflammation, and ferroptosis in the BTBR T+ tf/J mouse model of autism.

The aim of this study was to examine the effects of folic acid (FA) on the autistic phenotypes in BTBR T+ Itpr3tf/J (BTBR) mice and to investigate underlying mechanisms. Mice received FA (0.2 mg/kg/day) orally from postnatal days 14 to 35. Mice were then tested for stereotyped and repetitive behaviors, social interaction, and spatial learning and memory at the end of FA supplementation. Oxidative stress, neuroinflammatory responses and ferroptosis-related proteins in the brain were also evaluated. FA supplementation in BTBR mice reduced repetitive and stereotyped behavior, improved social communication, and enhanced memory and spatial learning. FA supplementation also reduced neuronal loss in hippocampal CA1 regions of the brain and decreased the levels of the proinflammatory cytokines such as interleukin-1ß (IL-1ß), Iba-1, IL-18, tumor necrosis factor-a, and IL-6 and glial fibrillary acidic protein in the hippocampus. FA supplementation changed the malondialdehyde and glutathione levels and superoxide dismutase (SOD) and glutathione peroxidase activities in the hippocampus. FA supplementation inhibited the elevation of the SOD1 and TFR protein levels and enhanced the relative expression levels of glutathione peroxidase 4 and ferroportin 1 in the hippocampus and increased the relative levels of phospho-Ca2+/calmodulin-dependent protein kinase II and phospho-cAMP-response element binding protein in the hippocampus. FA oral supplementation to BTBR mice rescued stereotyped and repetitive behaviors, social deficit, and spatial learning and memory impairments, likely by improving the oxidative-stress and inflammatory responses by altering the ferroptosis signaling pathways.