Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.
Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.
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DOI：
10.1002/jnr.23332
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发表时间：
2014-04
影响因子：
4.2
通讯作者：
Katz, Martin L.
中科院分区：
文献类型：
--
作者：
Morgan, Brandie R.;Coates, Joan R.;Johnson, Gayle C.;Shelton, G. Diane;Katz, Martin L.
犬退行性脊髓病（DM）是一种进行性多系统退行性疾病，与肌萎缩侧索硬化症（ALS）有许多共同特征。与某些形式的ALS一样，糖尿病与超氧化物歧化酶1 （SOD1）突变有关。临床症状包括盆腔肢体的全身性本体感觉性共济失调和痉挛性上运动神经元轻瘫，进而发展为弛缓性四肢瘫痪和吞咽困难。本研究的目的是将糖尿病定性为ALS的潜在疾病模型。我们之前报道了晚期糖尿病犬的肋间肌萎缩。为了确定胸运动单元（MU）的其他成分是否也表现出与功能障碍一致的形态变化，我们对DM影响的boxer和Pembroke Welsh corgi （PWCs）的胸脊髓运动神经元（MN）和背根神经节（DRG）以及运动和感觉神经根轴突进行了组织病理学和形态计量学分析。在两个品种中均未观察到MNs或运动根轴突的变化。然而，晚期PWCs表现出明显的感觉根轴突损失，许多DRG感觉神经元表现出退化的证据。这些结果表明，DM的肋间肌萎缩并不是由支配这些肌肉或其轴突的运动神经元的物理损失引起的。胸感觉根轴突丧失和感觉神经死亡提示感觉受累可能在糖尿病疾病进展中起重要作用。进一步分析导致这些形态学发现的机制将有助于开发针对糖尿病和某些形式的ALS的治疗干预措施。
Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
影响因子：
3.7
作者：
Forsberg K;Jonsson PA;Andersen PM;Bergemalm D;Graffmo KS;Hultdin M;Jacobsson J;Rosquist R;Marklund SL;Brännström T
通讯作者：
Brännström T
影响因子：
2.6
作者：
Coates, Joan R.;March, Philip A.;Williams, David A.
通讯作者：
Williams, David A.
影响因子：
4.2
作者：
King, A. E.;Dickson, T. C.;Vickers, J. C.
通讯作者：
Vickers, J. C.
DOI：
10.1073/pnas.0812297106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Awano, Tomoyuki;Johnson, Gary S.;Coates, Joan R.
通讯作者：
Coates, Joan R.