Abnormal repetitive behaviors in mice are associated with oxidative stress

(Press-News.org) Abnormal repetitive behaviors in mice are strongly linked to multiple biomarkers of oxidative stress, which occurs when antioxidants cannot counteract the effects of harmful molecules in the body, according to a study published November 5, 2025, in the open-access journal PLOS One by Kendall Coden and Dr. Joseph Garner of Stanford University, U.S. However, more research is needed to test whether antioxidants can prevent or treat these behaviors.

Stereotypies are abnormal, repetitive, and seemingly goal-less behaviors that are prevalent within the animal kingdom. They have been documented in nearly every captive mammal and bird species, including laboratory animals, zoo animals, and farm animals. In addition, they are a core feature of several human neurodevelopmental and neuropsychiatric disorders such as autism spectrum disorder and schizophrenia. Despite well documented environmental risk factors associated with stereotypies in captive animals, the developmental origins of these behaviors remain elusive.

Past research suggests that several neurodevelopmental and neuropsychiatric conditions are linked to REDOX imbalance -- a state in which physiological demand for antioxidants surpasses their bioavailability. Yet the relationship between REDOX imbalance and stereotypy has been unclear. To fill this knowledge gap, Coden, Garner and collaborators investigated whether REDOX imbalance is associated with the severity of stereotypies in mice. The researchers measured blood levels of the antioxidant glutathione -- a gold-standard biomarker of REDOX imbalance.

The results showed that glutathione levels were positively associated with stereotypy severity in young mice, but not old mice. Using a state-of-the-art proteomics approach, the researchers identified broader biomarker profiles of REDOX imbalance and stereotypy severity. As predicted, they found strong relationships between proteins linked to REDOX imbalance and both glutathione levels and stereotypy severity. Some of these associations were found only in young mice, and others were independent of age, suggesting that other factors contribute to stereotypies in old mice. These proteomics findings were replicated in a separate validation group of mice, indicating that these profiles are robust and independent of strain.

Taken together, these data indicate that REDOX imbalance may contribute to the developmental origins of stereotypy, highlighting novel targets for early detection and intervention. Moreover, the results suggest that plasma glutathione levels or levels of the identified protein biomarkers may serve as risk predictors for developing abnormal repetitive behaviors. According to the authors, the evolutionarily conserved nature of the proteins they identified suggests that the results have promising translational potential for clinical populations.

However, they caution that the results are correlational in nature, so it remains unclear whether REDOX imbalance is causally related to the development of stereotypy. Further investigation into the causal relationship between REDOX imbalance and stereotypy, and translation to other species such as humans, is required to confirm the generality of the results. In addition, more research is needed to determine whether antioxidant therapies can prevent or treat stereotypies in mice.

The authors add: “Our findings show that REDOX imbalance (greater demand for, than supply of antioxidants) is related to repetitive behaviors, and that specific proteins found in blood may provide a clearer, more precise way to measure this relationship. Many of the proteins identified in our study are also associated with neurodevelopmental and psychiatric conditions, suggesting that this set of proteins could help to guide development of novel diagnostic methods and treatments for disorders involving repetitive behaviors.”

“The great mystery with repetitive behaviors is that individuals differ so much in both risk and severity, even when they grow up in the same environment and share the same genetics," adds Garner, professor of comparative medicine, Stanford Medicine. “This mystery also gives us hope that repetitive behaviors might be preventable or curable. That’s why this work is such an exciting breakthrough, it gives us so many clues to follow, and a whole new technological approach to do so.”

 

 

In your coverage, please use this URL to provide access to the freely available article in PLOS One: http://plos.io/4hsaPHD

Citation: Coden KM, Beacham KJ, Stix-Brunell BE, Moorhead R, Byrd KA, Baker JN, et al. (2025) Stereotypy is strongly linked to multiple biomarkers of oxidative stress—A potential common etiology for Abnormal Repetitive Behaviors. PLoS One 20(11): e0326902. https://doi.org/10.1371/journal.pone.0326902

Author countries: U.S.

Funding: This project was supported by a Stanford Medicine Discovery Innovation Award to Dr. Joseph P. Garner. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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