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Preterm birth is associated with dystonic features and reduced cortical parvalbumin immunoreactivity in mice

Pediatric Research volume 97, pages 2475–2484 (2025)Cite this article

Abstract

Background

Preterm birth is a common cause of dystonia. Though dystonia is often associated with striatal dysfunction after neonatal brain injury, cortical dysfunction may best predict dystonia following preterm birth. Furthermore, abnormal sensorimotor cortex inhibition is associated with genetic and idiopathic dystonias. To investigate cortical dysfunction and dystonia following preterm birth, we developed a new model of preterm birth in mice.

Methods

We induced preterm birth in C57BL/6J mice at embryonic day 18.3, ~24 h early. Leg adduction variability and amplitude, metrics we have shown distinguish between dystonia from spasticity during gait in people with CP, were quantified from gait videos of mice. Parvalbumin-positive interneurons, the largest population of cortical inhibitory interneurons, were quantified in the sensorimotor cortex and striatum.

Results

Mice born preterm demonstrate increased leg adduction amplitude and variability during gait, suggestive of clinically observed dystonic gait features. Mice born preterm also demonstrate fewer parvalbumin-positive interneurons and reduced parvalbumin immunoreactivity in the sensorimotor cortex, but not the striatum, suggesting dysfunction of cortical inhibition.

Conclusions

These data may suggest an association between cortical dysfunction and dystonic gait features following preterm birth. We propose that our novel mouse model of preterm birth can be used to study this association.

Impact

  • Mouse models of true preterm birth are valuable for studying clinical complications of prematurity.

  • Mice born preterm demonstrate increased leg adduction amplitude and variability during gait, suggestive of clinically observed dystonic gait features.

  • Mice born preterm demonstrate fewer parvalbumin-positive interneurons and reduced parvalbumin immunoreactivity in the sensorimotor cortex, suggesting dysfunction of cortical inhibition.

  • Mice born preterm do not demonstrate changes in parvalbumin immunoreactivity in the striatum.

  • Cortical dysfunction may be associated with dystonic gait features following preterm birth.

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Fig. 1: Locomotion quantification.
Fig. 2: Gestational ages, litter sizes, and weights in mice born at term and preterm.
Fig. 3: Measures of locomotor impairment.
Fig. 4: Measures of clinically-validated dystonic gait features.
Fig. 5: Quantification of parvalbumin immunoreactivity in the sensorimotor cortex.
Fig. 6: Quantification of parvalbumin immunoreactivity in the striatum.

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Data availability

The authors confirm that the data supporting the findings of this study are available from qualified investigators upon request.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

Funding supporting this work is from the National Institutes of Neurological Disorders and Stroke: 1K08NS117850-01A1 (BRA) and 1R01NS112234 (RG).

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Author notes

  1. These authors contributed equally: Rafael Galindo, Bhooma R. Aravamuthan.

Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

    Kat Gemperli, Femi Folorunso, Benjamin Norin, Rebecca Joshua, Rachel Rykowski, Clayton Hill, Rafael Galindo & Bhooma R. Aravamuthan

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  1. Kat Gemperli
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  2. Femi Folorunso
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  8. Bhooma R. Aravamuthan
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Contributions

Kat Gemperli helped design the study, contributed to data collection, carried out data analyses, and critically reviewed and revised the manuscript. Femi Folorunso, Ben Norin, Rebecca Joshua, Rachel Rykowski, and Clayton Hill: contributed to data collection, carried out data analyses, and critically reviewed and revised the manuscript. Rafael Galindo helped design the study, supervised data collection, and critically reviewed and revised the manuscript. Bhooma Aravamuthan conceptualized and designed the study, supervised data collection and analysis, drafted the initial manuscript, and critically reviewed and revised the manuscript.

Corresponding author

Correspondence to Bhooma R. Aravamuthan.

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Gemperli, K., Folorunso, F., Norin, B. et al. Preterm birth is associated with dystonic features and reduced cortical parvalbumin immunoreactivity in mice. Pediatr Res 97, 2475–2484 (2025). https://doi.org/10.1038/s41390-024-03603-8

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