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Updated: May 10, 2026
A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
Ciliopathy interacts with neonatal anesthesia to cause non-apoptotic caspase-mediated motor deficits
Insights
Ketamine anesthesia can impair motor skills in newborns with genetic ciliopathies. This neurotoxicity is linked to altered neuronal connections and can be reversed by inhibiting caspase activity, suggesting a potential therapeutic target.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Anesthesia may cause developmental neurotoxicity, but its interaction with genetic predispositions is unclear.
- Children with congenital heart disease often have ciliary dysfunction and require neonatal anesthesia.
Purpose of the Study:
- To investigate how genetic ciliopathy influences anesthesia-induced neurotoxicity.
- To explore the role of caspase activation in ketamine-induced motor deficits.
Main Methods:
- Neonatal mice with ciliopathy were exposed to ketamine.
- Assessed motor skills, neocortical neuron apical spine density, and caspase activation.
- Investigated the effect of caspase suppression on neurodevelopmental outcomes.
Main Results:
- Ketamine exposure caused motor skill impairments in ciliopathic mice.
- These deficits were associated with reduced apical spine density and altered spine dynamics.
- Augmented non-apoptotic caspase activation was observed and linked to these changes.
- Caspase suppression rescued spine density and motor deficits.
Conclusions:
- Ciliopathy exacerbates ketamine-induced motor impairments.
- Sublethal caspase signaling is crucial for spine formation and motor learning.
- Caspase inhibition may reverse ketamine-induced neurodevelopmental deficits in vulnerable neonates.
Abstract:
Increasing evidence suggests that anesthesia may induce developmental neurotoxicity, yet the influence of genetic predispositions associated with congenital anomalies on this toxicity remains largely unknown. Children with congenital heart disease often exhibit mutations in cilia-related genes and ciliary dysfunction, requiring sedation for their catheter or surgical interventions during the neonatal period. Here we demonstrate that briefly exposing ciliopathic neonatal mice to ketamine causes motor skill impairments, which are associated with a baseline deficit in neocortical layer V neuron apical spine density and their altered dynamics during motor learning.. These neuromorphological changes were linked to augmented non-apoptotic neuronal caspase activation. Neonatal caspase suppression rescued the spine density and motor deficits, confirming the requirement for sublethal caspase signaling in appropriate spine formation and motor learning. Our findings suggest that ciliopathy interacts with ketamine to induce motor impairments, which is reversible through caspase inhibition. Furthermore, they underscore the potential for ketamine- induced sublethal caspase responses in shaping neurodevelopmental outcomes.
