通过损伤或疾病切断靶标后，鉴定具有恢复力的小鼠面部运动神经元群体。
Identification of a resilient mouse facial motoneuron population following target disconnection by injury or disease.
作者信息
Setter Deborah O, Haulcomb Melissa M, Beahrs Taylor, Meadows Rena M, Schartz Nicole D, Custer Sara K, Sanders Virginia M, Jones Kathryn J
机构信息
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Research and Development, Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA.
出版信息
Restor Neurol Neurosci. 2018;36(3):417-422. doi: 10.3233/RNN-170809.
BACKGROUND
When nerve transection is performed on adult rodents, a substantial population of neurons survives short-term disconnection from target, and the immune system supports this neuronal survival, however long-term survival remains unknown. Understanding the effects of permanent axotomy on cell body survival is important as target disconnection is the first pathological occurrence in fatal motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).
OBJECTIVE
The goal of this study was to determine if facial motoneurons (FMN) could survive permanent target disconnection up to 26 weeks post-operation (wpo) after facial nerve axotomy (FNA). In addition, the potentially additive effects of immunodeficiency and motoneuron disease on post-axotomy FMN survival were examined.
METHODS
This study included three wild type (WT) mouse strains (C57BL/6J, B6SJL, and FVB/NJ) and three experimental models (RAG-2-/-: immunodeficiency; mSOD1: ALS; Smn-/-/SMN2+/+: SMA). All animals received a unilateral FNA, and FMN survival was quantified at early and extended post-operative timepoints.
RESULTS
In the C57BL/6J WT group, FMN survival significantly decreased at 10 wpo (55±6%), and then remained stable out to 26 wpo (47±6%). In the RAG-2-/- and mSOD1 groups, FMN death occurred much earlier at 4 wpo, and survival plateaued at approximately 50% at 10 wpo. The SMA model and other WT strains also exhibited approximately 50% FMN survival after FNA.
CONCLUSION
These results indicate that immunodeficiency and motoneuron disease accelerate axotomy-induced neuron death, but do not increase total neuron death in the context of permanent target disconnection. This consistent finding of a target disconnection-resilient motoneuron population is prevalent in other peripheral nerve injury models and in neurodegenerative disease models as well. Characterization of the distinct populations of vulnerable and resilient motoneurons may reveal new therapeutic approaches for injury and disease.
背景
对成年啮齿动物进行神经横断时，大量神经元在与靶标短期断开连接后仍能存活，免疫系统支持这种神经元存活，但长期存活情况尚不清楚。了解永久性轴突切断对胞体存活的影响很重要，因为靶标断开连接是诸如肌萎缩侧索硬化症（ALS）和脊髓性肌萎缩症（SMA）等致命运动神经元疾病的首个病理事件。
目的
本研究的目的是确定面神经轴突切断术（FNA）后，面部运动神经元（FMN）在术后26周（wpo）能否在永久性靶标断开连接的情况下存活。此外，还研究了免疫缺陷和运动神经元疾病对轴突切断术后FMN存活的潜在累加效应。
方法
本研究包括三种野生型（WT）小鼠品系（C57BL/6J、B6SJL和FVB/NJ）和三种实验模型（RAG-2-/-：免疫缺陷；mSOD1：ALS；Smn-/-/SMN2+/+：SMA）。所有动物均接受单侧FNA，并在术后早期和延长时间点对FMN存活情况进行定量分析。
结果
在C57BL/6J野生型组中，FMN存活率在10 wpo时显著下降（55±6%），然后在26 wpo时保持稳定（47±6%）。在RAG-2-/-和mSOD1组中，FMN死亡在4 wpo时发生得更早，在10 wpo时存活率稳定在约50%。SMA模型和其他野生型品系在FNA后也表现出约50%的FMN存活率。
结论
这些结果表明，免疫缺陷和运动神经元疾病会加速轴突切断诱导的神经元死亡，但在永久性靶标断开连接的情况下不会增加神经元的总死亡数。在其他周围神经损伤模型和神经退行性疾病模型中，也普遍存在这种靶标断开连接后具有抗性的运动神经元群体这一一致发现。对易损和抗性运动神经元不同群体的特征描述可能会揭示损伤和疾病的新治疗方法。
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