Pathologic Involvement of Glutamatergic Striatal Inputs From the Cortices in TAR DNA-Binding Protein 43kDa-Related Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis.
Pathologic Involvement of Glutamatergic Striatal Inputs From the Cortices in TAR DNA-Binding Protein 43kDa-Related Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis.
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TAR DNA 结合蛋白 43kDa 相关的额颞叶变性和肌萎缩侧索硬化症中来自皮质的谷氨酸纹状体输入的病理学参与。
DOI：
10.1093/jnen/nlx055
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ishigaki S.
中科院分区：
文献类型：
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作者：
Riku Y;Watanabe H;Yoshida M;Mimuro M;Iwasaki Y;Masuda M;Ishigaki S.
在额颞叶变性(FTLD)和肌萎缩侧索硬化症(ALS)中，最近的研究假定认知能力下降和纹状体功能障碍之间的关系。纹状体通过从大脑皮层接受谷氨酸能输入来促进社会认知功能。然而，在这些疾病中，这些皮质-纹状体输入的脆弱性尚不清楚。本研究旨在探讨散发性TDP-43相关FTLD(FTLD-TDP)和ALS(ALS-TDP)患者大脑皮质谷氨酸能传入纹状体的情况。我们检查了46例连续尸检的患者(31例FTLD-TDP和15例ALS患者)和10名正常对照。用抗囊泡谷氨酸转运蛋白-1(VGLUT-1)免疫组织化学方法对纹状体谷氨酸能皮质-纹状体投射神经元的轴突终末进行定量。结果显示，所有FTLD-TDP患者的尾状头和壳核VGLUT-1阳性轴突终末均明显减少。尤其是C型病理的患者表现出严重的缺失。非痴呆性ALS患者的壳核VGLUT-1阳性轴突终末丢失，但尾状头VGLUT-1阳性轴突终末相对较少。共聚焦显微镜显示，部分患者的VGLUT-1阳性轴突终末内有TDP-43聚集。我们的结果表明，在TDP-43蛋白病的疾病谱中，来自大脑皮层的谷氨酸能纹状体输入与社会认知能力下降有关。
In frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), recent studies have presumed relationships between cognitive declines and striatal dysfunctions. The striatum contributes to socio-cognitive functions by receiving glutamatergic inputs from the cerebral cortices. However, the vulnerability of these cortico-striatal inputs is unclear in these diseases. This study aimed to evaluate the glutamatergic inputs to the striatum from the cerebral cortices in patients with sporadic TDP-43-related FTLD (FTLD-TDP) and ALS (ALS-TDP). We examined 46 consecutively autopsied patients (31 FTLD-TDP and 15 ALS patients) and 10 normal controls. The axon terminals of the glutamatergic cortico-striatal projection neurons were quantified at the striatum using antivesicular glutamate transporter-1 (VGLUT-1) immunohistochemistry. In results, all FTLD-TDP patients displayed marked depletion of VGLUT-1-positive axon terminals in the caudate head and putamen. Particularly, the patients with type C pathology showed a severe loss. The nondemented ALS patients displayed loss of VGLUT-1-positive axon terminals in the putamen, but those were relatively spared in the caudate head. Confocal microscopy revealed TDP-43 aggregations within VGLUT-1-positive axon terminals in a subset of the patients. Our results indicate marked involvement of glutamatergic striatal inputs from the cerebral cortices in association with socio-cognitive declines in a disease spectrum of TDP-43 proteinopathy.