# Ertugliflozin improves animal behaviours associated with oxidative stress and inflammation in a BTBR T + Itpr3tf/J mouse model of autism

## TL;DR

Ertugliflozin, a diabetes drug, reduces autism-like behaviors in mice by lowering oxidative stress and inflammation.

## Contribution

The study shows ertugliflozin's potential as a treatment for autism spectrum disorder by targeting oxidative stress and neuroinflammation.

## Key findings

- Ertugliflozin improved social interaction and reduced repetitive behaviors and anxiety in BTBR mice.
- The drug reduced oxidative stress markers and inhibited microglial activation in the brain.
- Ertugliflozin also prevented neuronal loss in the hippocampus and prefrontal cortex.

## Abstract

Autism spectrum disorder is a neurodevelopmental condition typified by difficulties in social interactions, repetitive and restricted behaviour and heightened anxiety. Increasing evidence suggests that oxidative stress and neuroinflammatory processes are crucial in the development of these behavioural abnormalities. Ertugliflozin, a sodium-glucose cotransporter-2 inhibitor approved by the FDA for treating type 2 diabetes mellitus, has also been reported to exert antioxidant and anti-inflammatory effects. BTBR T + Itpr3tf/J (BTBR) mice are widely used as a preclinical model of autism spectrum disorder, as they show core autism-like behavioural features. The present study investigated whether ertugliflozin could ameliorate autism spectrum disorder-like behaviour in BTBR mice and explored the associated mechanisms. It was found that ertugliflozin treatment significantly improved social interaction while reducing repetitive behaviours and anxiety-like responses compared with untreated BTBR mice. Ertugliflozin (20 mg/kg/day), administered orally, reduced neuronal loss in the CA1 region of the hippocampus and the prefrontal cortex. In addition, ertugliflozin reduced oxidative stress, as demonstrated by decreased malondialdehyde levels, restoration of glutathione content and improved activities of superoxide dismutase and catalase. A significant suppression of inflammatory cytokines accompanied these biochemical improvements. Furthermore, ertugliflozin significantly inhibited microglial activation in BTBR mice. Collectively, the findings indicate that ertugliflozin alleviates autism spectrum disorder-like behavioural deficits in BTBR mouse models, at least in part, by reducing oxidative stress and neuroinflammation. This study highlights ertugliflozin as a potential therapeutic candidate for the management of autism spectrum disorder.

Wang et al. demonstrate that ertugliflozin ameliorates core autism-like behaviour in BTBR T + Itpr3tf/J mice, improving social interaction while reducing repetitive behaviours and anxiety. These improvements correlate with attenuated neuronal loss, suppressed oxidative stress and reduced neuroinflammation. Our findings support ertugliflozin’s potential as a candidate for treating autism spectrum disorder.

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