Kimura Tadashi, Jiang Haishan, Konno Takuya, Seto Makiko, Iwanaga Keisuke, Tsujihata Mitsuhiro, Satoh Akira, Onodera Osamu, Kakita Akiyoshi, Takahashi Hitoshi
Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
Neuropathology. 2014 Aug;34(4):392-7. doi: 10.1111/neup.12105. Epub 2014 Jan 20.
Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP-43 or C9ORF72 mutation, of 12 years duration in a 75-year-old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP-43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP-43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non-motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP-43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP-43 inclusions.
布尼亚小体（BBs）是散发性肌萎缩侧索硬化症（SALS）患者剩余的下运动神经元（LMNs）中发现的小嗜酸性神经元胞质内含物（NCIs），是细胞病理学的一个特征性表现。我们检查了一例病程12年的SALS病例，该病例与TDP-43或C9ORF72突变无关，患者为一名75岁男性，已接受人工呼吸支持9年，表现为伴有TDP-43病理改变的广泛多系统退变。有趣的是，在该患者的动眼神经核、延髓网状结构和小脑齿状核中观察到许多类似BBs的NCIs。由于此前尚未描述过小脑齿状核中的BBs，我们对这些NCIs进行了超微结构和免疫组化研究，以进一步了解BBs的本质。在每个区域，这些NCIs的超微结构特征与先前在LMNs中描述的BBs相同。用抗胱抑素C（CC）和TDP-43的抗体对这三个区域以及相对保存较好的骶前角（S1和S2）和面神经运动核进行免疫染色。重要的是，结果显示，对CC具有免疫反应性的BBs是LMNs的特征，而非运动神经元则无此特征，并且在小脑齿状核中，有BBs和TDP-43内含物的神经元/有BBs的神经元的比例显著低于其他区域。这些发现表明，具有CC免疫反应性的BBs的出现与LMNs的特定细胞特性内在相关，并且BBs形成的机制与TDP-43内含物的形成机制不同。
