实验性肝性脑病大鼠小脑α-突触核蛋白表达上调。
Upregulation of alpha-synuclein expression in the rat cerebellum in experimental hepatic encephalopathy.
机构信息
Departamento de Biología Celular y Genética, Universidad de Alcalá, 28871 Madrid, Spain.
出版信息
Neuropathol Appl Neurobiol. 2010 Aug;36(5):422-35. doi: 10.1111/j.1365-2990.2010.01083.x. Epub 2010 Mar 22.
AIMS
The overexpression of alpha-synuclein has been associated with neurodegenerative diseases, especially when the protein aggregates to form insoluble structures. The present study examined the effect of chronic hyperammonaemia on alpha-synuclein expression in the rat cerebellum following portacaval anastomosis (PCA).
METHODS
Immunohistochemical and western blot determinations were performed 1 month and 6 months after the PCA procedure.
RESULTS
A time-dependent increase in alpha-synuclein expression was seen in the cerebellar grey matter compared with the controls. At 1 month post PCA, alpha-synuclein-immunopositive material was observed in the molecular layer, while the Purkinje cells showed weak alpha-synuclein expression, and alpha-synuclein aggregates were observed throughout the granular layer. At 6 months post PCA, alpha-synuclein expression was significantly increased compared with the controls. alpha-synuclein-immunostained astroglial cells were also found; the Bergmann glial cells showed alpha-synuclein-positive processes in the molecular layer of PCA-exposed rats, and in the granular layer, perivascular astrocytes showed intense alpha-synuclein immunoreactivity, as indicated by colocalization of alpha-synuclein with glial fibrillary acidic protein (GFAP). In addition, ubiquitin-immunoreactive inclusions were present in PCA-exposed rats, although they did not colocalize with alpha-synuclein. Western blotting performed at 6 months post PCA showed a reduction in the level of soluble alpha-synuclein compared with 1 month post PCA and the controls; this reduction was concomitant with an increase in the insoluble form of alpha-synuclein.
CONCLUSIONS
Although the precise mechanism by which alpha-synuclein aggregates in PCA-treated rats remains unknown, the present data suggest an important role for this protein in the onset and progression of hepatic encephalopathy, probably via its expression in astroglial cells.
目的
α-突触核蛋白的过表达与神经退行性疾病有关，尤其是当该蛋白聚集成不溶性结构时。本研究检测了门腔静脉吻合术（PCA）后慢性高氨血症对大鼠小脑α-突触核蛋白表达的影响。
方法
在 PCA 手术后 1 个月和 6 个月进行免疫组织化学和 Western blot 测定。
结果
与对照组相比，在小脑灰质中观察到α-突触核蛋白表达的时间依赖性增加。在 PCA 后 1 个月，在分子层中观察到α-突触核蛋白免疫阳性物质，而浦肯野细胞显示出较弱的α-突触核蛋白表达，并且在颗粒层中观察到α-突触核蛋白聚集物。在 PCA 后 6 个月，与对照组相比，α-突触核蛋白表达显著增加。还发现了α-突触核蛋白免疫染色的星形胶质细胞；在暴露于 PCA 的大鼠的分子层中，Bergmann 胶质细胞显示出α-突触核蛋白阳性过程，在颗粒层中，血管周围星形胶质细胞显示出强烈的α-突触核蛋白免疫反应性，如α-突触核蛋白与神经胶质纤维酸性蛋白（GFAP）的共定位所示。此外，在暴露于 PCA 的大鼠中存在泛素免疫反应性包含物，尽管它们与α-突触核蛋白不共定位。在 PCA 后 6 个月进行的 Western blot 分析显示，与 PCA 后 1 个月和对照组相比，可溶性α-突触核蛋白水平降低；这种减少伴随着不溶性α-突触核蛋白形式的增加。
结论
尽管 PCA 处理大鼠中α-突触核蛋白聚集的确切机制尚不清楚，但目前的数据表明，该蛋白在肝性脑病的发生和进展中可能发挥重要作用，可能通过其在星形胶质细胞中的表达。
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