Mice born preterm develop gait dystonia and reduced cortical parvalbumin immunoreactivity.
Mice born preterm develop gait dystonia and reduced cortical parvalbumin immunoreactivity.
复制标题
早产小鼠出现步态肌张力障碍并降低皮质小白蛋白免疫反应性。
DOI：
10.1101/2024.02.01.578353
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Aravamuthan,BhoomaR
中科院分区：
文献类型：
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作者：
Gemperli,Kat;Folorunso,Femi;Norin,Benjamin;Joshua,Rebecca;Hill,Clayton;Rykowski,Rachel;Galindo,Rafael;Aravamuthan,BhoomaR
早产导致脑性瘫痪（CP）是儿童肌张力障碍的最常见原因，这是一种使人衰弱且通常难以治疗的运动障碍。肌张力障碍通常与纹状体胆碱能中间神经元的功能障碍有关，但临床成像数据表明，皮质损伤可能是早产后肌张力障碍的最佳预测因素。此外，在许多非CP肌张力障碍的研究中发现了异常的感觉运动皮层抑制。为了评估早产后肌张力障碍的皮质病因的可能性，我们开发了一种新的小鼠早产模型。注意到在C57 BL/6 J背景下小鼠的足月分娩是胚胎第19.1天（E19.1），我们在胚胎第（E）18.3天（相当于人类妊娠22周）在幼仔存活极限下诱导早产。早产小鼠在步态期间显示临床验证的肌张力障碍指标（腿内收幅度和变异性），并且还显示感觉运动皮质中的小清蛋白免疫反应性降低，表明皮质小清蛋白阳性抑制性中间神经元功能障碍。值得注意的是，在纹状体中未观察到小清蛋白免疫反应性降低或小清蛋白阳性神经元数量变化。这些数据支持早产后皮质功能障碍和肌张力障碍之间的关联。我们建议我们的早产小鼠模型可用于研究这种关联，并可能研究极端早产的其他后遗症。
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.