Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by impaired social interactions, stereotypical repetitive behavior and restricted interests. Although the global incidence of ASD has increased over time, the etiology of ASD is poorly understood, and there is no effective pharmacological intervention for treating ASD. Recent studies have suggested that metformin has the potential to treat ASD. Thus, in this study, we assessed the therapeutic effects of early metformin treatment in a BTBR T+ Itpr3tf/J (BTBR) mouse model of ASD. We observed that early metformin administration significantly reversed social approach deficits, attenuated repetitive grooming and reduced marble burying in BTBR mice. Metformin did not change the general locomotor activity or anxiety-like behavior in both BTBR and C57BL/6J (B6) mice. Our findings suggest that early metformin treatment may have beneficial effects on ameliorating behavioral deficits in ASD.
Highlights
Autism spectrum disorders (ASDs) are a cluster of neurodevelopmental disabilities characterized by defective social interactions, impaired communication and restricted and repetitive behaviors (Leekam et al, 2011; Fakhoury, 2015)
The major results of this study reveal that neonatal metformin treatments, administered from P7 to P14, can improve social interaction and reduce some repetitive behaviors in BTBR mice
Our study suggests that metformin treatment, during neonatal development, might play a role in preventing some of the behavioral abnormalities associated with ASD and that the BTBR mouse model can be a promising model for the preclinical screening of suitable drugs
Summary
Autism spectrum disorders (ASDs) are a cluster of neurodevelopmental disabilities characterized by defective social interactions, impaired communication and restricted and repetitive behaviors (Leekam et al, 2011; Fakhoury, 2015). It was demonstrated that metformin crosses the blood brain barrier and it was amply demonstrated to prevent diabetes-induced memory deficits in rats (Mousavi et al, 2015), and modulate cognitive functional abnormalities in several neuropsychiatric disorders (Hsu et al, 2011; Dy et al, 2018). In depressed patients with diabetes mellitus, chronic treatment with metformin has antidepressant behavioral effects through improvements in cognitive performance (Guo et al, 2014). One clinical study conducted by Dy et al (2018) has shown that metformin treatment could cause consistent alleviation in social responsiveness, social avoidance, irritability and hyperactivity in individuals with fragile X syndrome (FXS), the leading inherited cause of intellectual disability and ASD, without significant side-effects
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