Gibson S J, Polak J M, Katagiri T, Su H, Weller R O, Brownell D B, Holland S, Hughes J T, Kikuyama S, Ball J
Department of Histochemistry, Royal Postgraduate Medical School, London, U.K.
Brain Res. 1988 Dec 6;474(2):255-78. doi: 10.1016/0006-8993(88)90440-4.
The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn. Numerous somatostatin-immunoreactive cell bodies were also present. In the ventral horn, immunoreactive fibres were less abundant. Most motoneurones were closely apposed by fibres immunoreactive for enkephalin, neurokinin, somatostatin and thyrotrophin-releasing hormone (TRH). A subpopulation of motoneurones, most notable in lumbar segments, displayed CGRP immunoreactivity. In common with autonomic nuclei, Onuf's nucleus, which is thought to innervate perineal striated muscle and external urethral and anal sphincters, was densely innervated with CPON-, enkephalin-, and in particular somatostatin-immunoreactive fibres, thus suggesting Onuf's nucleus may have an autonomic component. In the diseased cords, there was a reduction in the area of the ventral horn and numbers of motoneurones as revealed by conventional histological staining and immunostaining of neurofilament triplet proteins. No changes in the distribution of peptides was noted in the dorsal horn or autonomic nuclei. By contrast, in the ventral horn, neurokinin-, enkephalin-, somatostatin- and TRH-immunoreactive fibres, which are normally found associated with motoneurones, were absent. Therefore, not only are motoneurones lost in MND, but also the fibres which innervate them. CGRP-immunoreactive motoneurones were not observed, a finding consistent with the proposed role of this peptide as a muscle-trophic factor. In contrast to the large motoneurone groups in the ventral horn, the neuronal integrity of Onuf's nucleus and the peptides associated with it were spared. These data further imply that Onuf's nucleus is not a typical motor nucleus and it is not purely somatic. The coincident loss of peptide immunoreactivity and motoneurones from the large motor nuclei and sparing of Onuf's nucleus and its peptide-containing constituents in the diseased state suggests that peptides contribute to maintenance of neural integrity.
在52例神经功能正常的病例中，研究了8种肽在脊髓4个主要节段水平（颈段、胸段、腰段、骶段）的分布情况。采用相同方法，对36例运动神经元病（MND）患者的类似脊髓区域进行比较，以确定与感觉、运动和自主神经功能相关区域中肽分布的可能变化。在正常脊髓中，降钙素基因相关肽（CGRP）、神经肽Y的C端侧翼肽（CPON）、脑啡肽、甘丙肽、神经激肽样肽、生长抑素和血管活性肠肽（VIP）免疫反应性纤维在背角丰富。也存在大量生长抑素免疫反应性细胞体。在腹角，免疫反应性纤维较少。大多数运动神经元紧密相邻着脑啡肽、神经激肽、生长抑素和促甲状腺激素释放激素（TRH）免疫反应性纤维。运动神经元的一个亚群，在腰段最为显著，显示出CGRP免疫反应性。与自主神经核一样，被认为支配会阴横纹肌以及尿道外括约肌和肛门括约肌的奥努夫核，被CPON、脑啡肽，尤其是生长抑素免疫反应性纤维密集支配，因此提示奥努夫核可能有自主神经成分。在患病脊髓中，传统组织学染色和神经丝三联蛋白免疫染色显示腹角面积减小，运动神经元数量减少。在背角或自主神经核中未观察到肽分布的变化。相比之下，在腹角，通常与运动神经元相关的神经激肽、脑啡肽、生长抑素和TRH免疫反应性纤维缺失。因此，在MND中不仅运动神经元丢失，而且支配它们的纤维也丢失。未观察到CGRP免疫反应性运动神经元，这一发现与该肽作为肌肉营养因子的假定作用一致。与腹角中的大运动神经元群不同，奥努夫核及其相关肽的神经元完整性得以保留。这些数据进一步表明奥努夫核不是典型的运动核，也不纯粹是躯体性的。在患病状态下，大运动核中肽免疫反应性和运动神经元同时丢失，而奥努夫核及其含肽成分得以保留，这表明肽有助于维持神经完整性。
