Glial pathology in neuronal cell death

神经细胞死亡中的胶质病理学

• 批准号: 11670201
• 负责人: KOMORI Takashi
• 金额: $ 2.37万
• 依托单位: Tokyo Metropolitan Institute for Neuroscience
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670201/
• 关键词: multiple system atrophy; progressive supranuclear palsy; oligodendrocyte; astrocyte; cytoplasmic inclusions; cell death; tau; 14-3-3; 神経細胞死; タウ蛋白; グリア細胞; ピック病; タウオパチー; 神経細胞変性; 大脳基底核変性症; グリア; 剖検脳

To investigate whether glial pathology correlates with neurodegeneration, we studied autopsied material from subjects with neurodegenerative diseases including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease (PiD) and multiple system atrophy (MSA). Results: 1) Correlation between tau density and cerebral tissue damage were analyzed in 7 PSP. Low negative correlation with MAP-2 or EAAT-1 densities and low positive correlation with CD68 or GFAP densities were obtained. Cerebral tissue injury may be not dependent on the amount of tau in PSP. 2) Hippocampal tau pathology was studied in 6 PSP, 4 CBD and 3 age-matched controls. In PSP and control, neurofibrillary tangles and threads were present in the entorhinal cortex and hippocampus. In CBD, coiled bodies and threads were found in the alveus and stratum lacunosum and tau-positive grains in the inner molecular layer of the dentate gyrus. Hippocampal tau pathology in PSP is similar to that in aged subje … More cts whereas that in CBD is distinctive from PSP. 3) Using tyramide signal amplification system on anti-PHF-tau antibody in 5 PiD, ***ead and Pick body-like inclusions were detected in the subcortical white matter. Hyperphosphorylated tau may be localized in the subcortical axons in addition to the dendrites. 4) Immunohistologic examination using microglial markers were studied in13 MSA and disclosed numerous amoeboid microglia phagocytosing degenerating myelin. Such activated microglia were the most prominent in the extrapyramidal and cerebellar input systems. Microglial activation may play a role in the system degeneration of MSA. 5) In 6 MSA, co-localization of 14-3-3-protein and alpha-synuclein immunoreactivities within the GCIs was confirmed on immunohistochemistry. The immunolabeling rate of GCIs with 14-3-3 proteins varied regionally from 40 to 90 %. Negative correlation between tissue degeneration and density of 14-3-3-positive GCIs was present. 14-3-3 proteins may be closely associated with alpha-synuclein in GCIs Less

为了研究神经胶质病理学是否与神经变性相关，我们研究了来自神经退行性疾病的受试者的尸检材料，包括进行性超跨性麻痹（PSP），皮质性生蛋白变性（CBD），PICK'S病（PID）（PID）（PID）和多系统萎缩（MSA）。结果：1）在7 PSP中分析了Tau密度与脑组织损伤之间的相关性。与MAP-2或EAAT-1密度的低负相关性以及与CD68或GFAP密度的低正相关性。脑组织损伤可能不依赖于PSP中的tau量。 2）在6个PSP，4 CBD和3个年龄匹配的对照中研究了海马TAU病理学。在PSP和对照中，内嗅皮层和海马中存在神经纤维缠结和线。在CBD中，在牙齿回和牙齿的内分子层中发现了盘绕的物体和螺纹。 PSP中的海马tau病理与年龄级别相似……更多的CTS，而CBD中的tau病理与PSP不同。 3）在5个PID中使用泰酰胺信号扩增系统在抗PHF-TAU抗体上，在皮层白质中检测到*** eDEAD和拾取体状夹杂物。除4）使用小胶质细胞标记的免疫组织学检查外，还可以将高磷酸化的TAU定位在13 MSA中，并披露了许多变性小胶质细胞吞噬髓磷脂。这种活化的小胶质细胞是腹膜外和小脑输入系统中最突出的小胶质细胞。小胶质细胞激活可能在MSA的系统变性中起作用。 5）在6 MSA中，在免疫组织化学上证实了GCIS内14-3-3-蛋白质和α-核蛋白免疫反应性的共定位。 14-3-3蛋白的GCI的免疫标记速率从40％到90％变化。组织变性与密度之间的负相关性为14-3-3阳性GCI。 14-3-3蛋白可能与GCIS中的α-核蛋白密切相关

项目成果

ishizawa K, Komori T, Shimazu T, et al.: "Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann-Straussler-Scheinker syndrome P102L mutation complicated with dementia"Acta Neuropathologica. 104. 342-350 (2002)

ishizawa K、Komori T、Shimazu T 等人：“在 Gerstmann-Straussler-Scheinker 综合征 P102L 突变并发痴呆的病例中，过度磷酸化 tau 沉积与朊病毒蛋白负荷平行”《神经病理学报》。

Paul Kleihues 他: "Pathology and Genetics of Tumours of the nervous System"International Society of Neuropathology. (2000)

Paul Kleihues 等人：“神经系统肿瘤的病理学和遗传学”国际神经病理学学会（2000）。

Komori T, Arai N, Shimizu H, et al.: "Cortical perivascular satellitosiss in intractable epilepsy ; a form of cortical dysplasia?"Acta Neuropathologica. 104. 149-154 (2002)

Komori T、Arai N、Shimizu H 等人：“顽固性癫痫中的皮质血管周围卫星沉积症；皮质发育不良的一种形式？”《神经病理学报》。

Komori T, Ishizawa K, Arain N, et al.: "Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy"Acta Neuropathologica. in press.

Komori T、Ishizawa K、Arain N 等人：“多系统萎缩的胶质细胞质内含物中 14-3-3 蛋白的免疫表达”《神经病理学报》。

Komori T, et al.: "Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy"Acta Neuropathologica. (In press).

Komori T 等人：“多系统萎缩的胶质细胞质内含物中 14-3-3 蛋白的免疫表达”《神经病理学报》。