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Updated: Jul 3, 2025
Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease
Published on: July 18, 2019
Mice born preterm develop gait dystonia and reduced cortical parvalbumin immunoreactivity
Kat Gemperli1, Femi Folorunso1, Benjamin Norin1
1Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Insights
Preterm birth causes cerebral palsy (CP) and dystonia. New mouse models show preterm birth is linked to cortical dysfunction, not striatal, suggesting a new avenue for treating this movement disorder.
Area of Science:
- Neuroscience
- Developmental Biology
- Movement Disorders
Background:
- Cerebral palsy (CP) from preterm birth is a leading cause of childhood dystonia, a movement disorder.
- While striatal cholinergic interneurons were implicated, cortical injury may better predict dystonia post-preterm birth.
- Abnormal sensorimotor cortex inhibition is noted in non-CP dystonias.
Approach:
- Developed a novel mouse model of preterm birth at embryonic day 18.3 (equivalent to 22 weeks gestation).
- Assessed preterm mice for clinically validated dystonia metrics during gait.
- Examined parvalbumin immunoreactivity in the sensorimotor cortex and striatum.
Key Points:
- Preterm mice exhibited dystonia-like gait abnormalities.
- Reduced parvalbumin immunoreactivity was observed in the sensorimotor cortex of preterm mice.
- No significant changes in parvalbumin immunoreactivity were found in the striatum.
Conclusions:
- Data support a link between sensorimotor cortex dysfunction and dystonia following preterm birth.
- The developed mouse model offers a platform for studying preterm birth sequelae, including dystonia.
- Findings suggest targeting cortical mechanisms may be beneficial for treating preterm birth-associated dystonia.
Abstract:
Preterm birth leading to cerebral palsy (CP) is the most common cause of childhood dystonia, a movement disorder that is debilitating and often treatment refractory. Dystonia has been typically associated with dysfunction of striatal cholinergic interneurons, but clinical imaging data suggests that cortical injury may best predict dystonia following preterm birth. Furthermore, abnormal sensorimotor cortex inhibition has been found in many studies of non-CP dystonias. To assess the potential for a cortical etiology of dystonia following preterm birth, we developed a new model of preterm birth in mice. Noting that term delivery in mice on a C57BL/6J background is embryonic day 19.1 (E19.1), we induced preterm birth at the limits of pup viability at embryonic day (E) 18.3, equivalent to human 22 weeks gestation. Mice born preterm demonstrate display clinically validated metrics of dystonia during gait (leg adduction amplitude and variability) and also demonstrate reduced parvalbumin immunoreactivity in the sensorimotor cortex, suggesting dysfunction of cortical parvalbumin-positive inhibitory interneurons. Notably, reduced parvalbumin immunoreactivity or changes in parvalbumin-positive neuronal number were not observed in the striatum. These data support the association between cortical dysfunction and dystonia following preterm birth. We propose that our mouse model of preterm birth can be used to study this association and potentially also study other sequelae of extreme prematurity.
