运动神经元病与TDP-43蛋白的病理性表达

The pathological TDP-43 protein expression in the central nervous system of motor neuron disease

目的 认识TDP-43蛋白在运动神经元病中枢神经系统的病理性表达特征.方法 对4例经尸检病理证实的运动神经元病的临床及病理组织学特征进行总结;并对其脑和脊髓切片进行泛素、磷酸化TDP-43免疫组化染色,观察其阳性表达情况,并与同年龄、无神经疾病病史的3例病例的脑和脊髓组织进行对照.结果 4例病例具有运动神经元病典型的临床与组织学特征,其脑和脊髓组织中,3例存在神经元泛素阳性包涵体结构,主要表现为丝团样包涵体,致密圆形包涵体及路易样包涵体;2例存在明确的TDP-43阳性表达,表现为广泛分布于大脑运动皮层及脊髓前角的各种形态的神经元胞浆包涵体及胶质细胞包涵体,1例存在脊髓前角神经元TDP43弱阳性表达.对照病例无泛素阳性及TDP-43阳性包涵体发现.结论 运动神经元病患者的中枢神经系统存在广泛TDP-43蛋白阳性表达,且其阳性包涵体具有一定特征性,值得进一步研究其形成机制.

Objective To understand pathological TDP-43 features in the central nervous systems of patients with clinically and autopsy confirmed motor neuron disease （MND）.Methods The clinical and histopathological features of 4 cases with MND confirmed by autopsy were summarized; anti-ubiquitin （Ub） and anti-TDP-43 immunohistochemical staining were carried out on tissue of brains and spinal cords from 4 cases with MND and 3 control cases without history of neurological disorders.Results These 4 cases presented with typical clinical and histologic features of MND.Ub-positive inclusions were observed in brain and spinal cord from 3 cases with the Ub-positive inclusions of skein-round-and lewy body-like structures.Strong TDP-43 pathological staining in brain and spinal cord was identified in 2 cases with MND presented as neuronal and glial cytoplasmic inclusions with various shapes.The TDP-43 positive inclusions were widely distributed in the motor cortex of brain and the anterior horn of spinal cord.TDP-43 weak staining in the spinal cord tissue was observed in 1 case with MND.No Ub-and TDP-43 positive inclusions were found in 3 control cases.Conclusion There is widespread pathological TDP-43 expression in the central nervous system of MND.TDP-43 positive inclusions in MND have relatively high specificity.It is worth further study on their formation mechanism.