Metformin Partially Lessens Autism-Related Behaviors in Mice Subjected to Maternal Separation Stress by Combating Hippocampal Neuroinflammation and Oxidative Stress Imbalance.

Researchers tested whether metformin (a diabetes medication) could help with autism-like behaviors in mice. The mice were stressed early in life by separating them from their mothers, which can cause autism-like symptoms. After giving metformin to the mice for two weeks, researchers found improvements in social behavior, memory, and reduced repetitive actions. The medication also reduced brain inflammation and cell damage. This is early research in animals only.

This animal study investigated metformin's effects on autism-related behaviors in mice subjected to maternal separation stress, an early-life stressor linked to ASD development. Forty male mice were divided into control and treatment groups, with metformin administered at various doses (100-300 mg/kg) for two weeks. Behavioral assessments included social interaction, memory, and repetitive behavior tests. Results showed metformin improved social preference and interaction, enhanced passive avoidance memory, and reduced repetitive behaviors.

Biochemical analysis revealed metformin decreased hippocampal oxidative stress markers (MDA, nitrite) and inflammatory cytokine gene expression (TLR4, TNF-α, IL-1β, NLRP3). The findings suggest metformin may alleviate autism-related behaviors through anti-inflammatory and antioxidant mechanisms in the hippocampus.

While promising for understanding neuroinflammatory mechanisms in autism, this preclinical research requires human studies before clinical application. Results suggest metformin's anti-inflammatory properties may warrant investigation as adjunct therapy, but safety and efficacy in autistic individuals remains unknown.

Animal study with limited generalizability to humans. Small sample size (40 mice). Short treatment duration (2 weeks). Unclear methodology details. No long-term follow-up. Single stress model may not represent full autism spectrum complexity.

Autism spectrum disorder (ASD) is a neurological condition with growing global prevalence. One of the important factors involved in the pathophysiology of ASD is experiencing stress during early life, such as maternal separation (MS). Metformin, a well-founded glucose-lowering agent, possesses neuroprotective properties. This research aims to investigate the effects of metformin on autism-related behaviors in MS mice, with a focus on its probable effects on ameliorating hippocampal oxidative stress imbalance and neuroinflammation.

In this study, 40 male mice were randomly assigned to five experimental groups. The control group received an intraperitoneal injection of normal saline (10 ml/kg), while normal saline (10 ml/kg) or metformin at doses of 100, 200, and 300 mg/kg were injected into the MS mice for 2 weeks. Behavioral trials, including the three-chamber sociability test, the shuttle box test, and the marble burying test (MBT) were conducted to evaluate autism-related behaviors. Malondialdehyde (MDA), nitrite, total antioxidant capacity (TAC), and expression of inflammatory cytokines including TLR4, TNF-α, IL-1β, and NLRP3 at the gene level were evaluated in the hippocampus.

The results revealed that metformin enhanced the social preference index (SPI) and sociability index (SI) in the three-chamber test, improved passive avoidance memory in the shuttle box test, and reduced repetitive behaviors as assessed by the MBT. Furthermore, metformin decreased hippocampal levels of nitrite, MDA and the gene expression of inflammatory cytokines. In conclusion, metformin appears to alleviate autism-related behaviors in MS mice, possibly through combating oxidative stress imbalance and mRNA expression of inflammatory cytokines within the hippocampus.