2025-08-14 ワシントン大学セントルイス校
<関連情報>
- https://source.washu.edu/2025/08/new-method-more-accurately-assesses-movement-disorder-in-children/
- https://medicine.washu.edu/news/new-method-more-accurately-assesses-movement-disorder-in-children/
- https://onlinelibrary.wiley.com/doi/10.1002/ana.27299
慢性的な線条体コリン作動性中間神経細胞の興奮が、マウスにおいて脳性麻痺に関連する痙攣性行動を引き起こす Chronic Striatal Cholinergic Interneuron Excitation Causes Cerebral Palsy-Related Dystonic Behavior in Mice
Kat Gemperli BA, Xinguo Lu PhD, Keerthana Chintalapati BA, Alyssa Rust BS, Rishabh Bajpai PhD, Nathan Suh, Joanna Blackburn MD, Rose Gelineau-Morel MD, Michael C. Kruer MD …
Annals of Neurology Published: 03 July 2025
DOI:https://doi.org/10.1002/ana.27299
Graphical Abstract
Abstract
Objective
Mouse models of genetic dystonias have demonstrated abnormal striatal cholinergic interneuron excitability, but do not consistently demonstrate subjective dystonic features. To determine whether striatal cholinergic interneuron excitation can cause potentially dystonic motor behaviors, we first determined features correlated specifically with dystonia severity in people and then determined whether these features emerged in mice following striatal cholinergic interneuron excitation.
Methods
Eight movement disorders experts rated dystonia severity in 193 videos of people with cerebral palsy doing a seated task. Leg adduction variability metrics, which are known to correlate with leg dystonia severity during gait, were quantified in these videos of seated tasks. Metrics significantly associated with leg dystonia severity during seated tasks in people were then quantified in mice and compared between mice who underwent chemogenetic striatal cholinergic interneuron excitation (n = 17) and mice who did not (n = 17).
Results
Leg adduction variability correlated well with experts’ leg dystonia severity scores in people. Leg adduction variability was also significantly increased in mice that underwent striatal cholinergic interneuron excitation compared to mice that did not (p < 0.05). This difference was not present with acute excitation and emerged only after 14 days of ongoing excitation.
Interpretation
We demonstrate that leg adduction variability correlates with leg dystonia severity in people with cerebral palsy and that chronic, but not acute, striatal cholinergic interneuron excitation can cause leg adduction variability in mice. These results support targeting striatal cholinergic interneurons for dystonia drug development and demonstrate the potential value of using quantifiable leg adduction metrics to study dystonia pathophysiology. ANN NEUROL 2025
