Differences in lumbar motor neuron pruning in an animal model of early onset spasticity
Differences in lumbar motor neuron pruning in an animal model of early onset spasticity
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DOI：
10.1152/jn.00186.2018
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发表时间：
2018-08-01
影响因子：
2.5
通讯作者：
Sieck, Gary C.
中科院分区：
文献类型：
--
作者：
Brandenburg, Joline E.;Gransee, Heather M.;Sieck, Gary C.
运动神经元(MN)在早发性痉挛中的发育尚不清楚。例如，痉挛性脑瘫(SCP)。儿童时期最常见的运动障碍，通过脑成像预测很差，但研究仍然集中在大脑上。相比之下，MNS通过运动单位和神经递质信号，成为大多数痉挛治疗的靶点，是运动控制的最终共同输出。SCP中MN的发育是一个关键的知识鸿沟，因为胚胎晚期和出生后不仅是假想的脑损伤发生的时候，也是脊髓神经运动发育的关键时期。使用早发性痉挛的动物模型[带有甘氨酸(Gly)受体突变的Spa小鼠(B6.Cg.-Girb(Spa)/J])，我们假设在发育过程中移除有效的甘氨酸能神经递质输入到MN将影响MN的修剪(包括初级树突)和MN大小。SpA(Glrb-/-)和野生型(Glrb+/+)小鼠，4~9wk，经腓神经四甲基罗丹明浸泡，逆行标记胫前肌MNS。3天后，处死小鼠，用4%多聚甲醛灌流，取出脊髓进行共聚焦成像。SpA鼠的腰椎胫骨前肌MN减少了61%(P<；0.01)，对较大的MN的影响不成比例。此外，观察到胫骨前侧MN索马里表面积减少了23%(P=0.046)，初级树突增加了12%(P=0.05)。因此，MN修剪和MN躯体表面积在早发性痉挛中是异常的。更少和更小的MN可能与痉挛表型有关。新发现和值得注意的运动神经元(MN)在早发性痉挛中的发展尚不清楚。在早发性痉挛的动物模型SpA小鼠中，我们发现与对照组相比，腰椎胫骨前肌MN减少了61%。这种MN损失对较大的MN造成了不成比例的影响。因此，SpA小鼠MN池的数量和异质性减少，可能是导致痉挛表型的原因之一。
Motor neuron (MN) development in early onset spasticity is poorly understood. For example, spastic cerebral palsy (sCP). the most common motor disability of childhood, is poorly predicted by brain imaging, yet research remains focused on the brain. By contrast, MNs, via the motor unit and neurotransmitter signaling, arc the target of most therapeutic spasticity treatments and are the final common output of motor control. MN development in sCP is a critical knowledge gap, because the late embryonic and postnatal periods are not only when the supposed brain injury occurs but also are critical times for spinal cord neuromotor development. Using an animal model of early onset spasticity [spa mouse (B6.Cg.-GIrb(spa)/J) with a glycine (Gly) receptor mutation], we hypothesized that removal of effective glycinergic neurotransmitter inputs to MNs during development will influence MN pruning (including primary dendrites) and MN size. Spa (Glrb-/-) and wildtype (Glrb+/+) mice, ages 4-9 wk, underwent unilateral retrograde labeling of the tibialis anterior muscle MNs via peroneal nerve dip in tetramethylrhodamine. After 3 days, mice were euthanized and perfused with 4% paraformaldehyde, and the spinal cord was excised and processed for confocal imaging. Spa mice had similar to 61% fewer lumbar tibialis anterior MNs (P < 0.01), disproportionately affecting larger MNs. Additionally, a similar to 23% reduction in tibialis anterior MN somal surface area (P < 0.01) and a 12% increase in primary dendrites (P = 0.046) were observed. Thus MN pruning and MN somal surface area arc abnormal in early onset spasticity. Fewer and smaller MNs may contribute to the spastic phenotype.NEW & NOTEWORTHY Motor neuron (MN) development in early onset spasticity is poorly understood. In an animal model of early onset spasticity, spa mice, we found similar to 61% fewer lumbar tibialis anterior MNs compared with controls. This MN loss disproportionately affected larger MNs. Thus number and heterogeneity of the MN pool are decreased in spa mice, likely contributing to the spastic phenotype.