Suárez Isabel, Bodega Guillermo, Rubio Miguel, Fernández Benjamín
Departamento de Biomedicina y Biotecnología, Universidad de Alcalá, Madrid, Spain.
Departamento de Biología Celular, Universidad Complutense, Madrid, Spain.
Restor Neurol Neurosci. 2017;35(5):469-481. doi: 10.3233/RNN-170728.
The present work examines α-synuclein expression in the nigrostriatal system of a rat chronic hepatic encephalopathy model induced by portacaval anastomosis (PCA). There is evidence that dopaminergic dysfunction in disease conditions is strongly associated with such expression. Possible relationships among dopaminergic neurons, astroglial cells and α-synuclein expression were sought.
Brain tissue samples from rats at 1 and 6 months post-PCA, and controls, were analysed immunohistochemically using antibodies against tyrosine hydroxylase (TH), α-synuclein, glial fibrillary acidic protein (GFAP) and ubiquitin (Ub).
In the control rats, TH immunoreactivity was detected in the neuronal cell bodies and processes in the substantia nigra pars compacta (SNc). A dense TH-positive network of neurons was also seen in the striatum. In the PCA-exposed rats, however, a reduction in TH-positive neurons was seen at both 1 and 6 months in the SNc, as well as a reduction in TH-positive fibres in the striatum. This was coincident with the appearance of α-synuclein-immunoreactive neurons in the SNc; some of the TH-positive neurons also showed α-synuclein immunoreactivity. In addition, α-synuclein accumulation was seen in the SNc and striatum at both 1 and 6 months post-PCA, whereas α-synuclein was only mildly expressed in the nigrostriatal pathway of the controls. Astrogliosis was also seen following PCA, as revealed by increased GFAP expression from 1 month to 6 months post-PCA in both the SN and striatum. The astroglial activation level in the SN paralleled the reduced neuronal expression of TH throughout PCA exposure.
α-synuclein accumulation following PCA may induce dopaminergic dysfunction via the downregulation of TH, as well as astroglial activation.
本研究检测了门腔静脉吻合术（PCA）诱导的大鼠慢性肝性脑病模型黑质纹状体系统中α-突触核蛋白的表达。有证据表明，疾病状态下的多巴胺能功能障碍与这种表达密切相关。本研究探寻了多巴胺能神经元、星形胶质细胞和α-突触核蛋白表达之间可能的关系。
使用抗酪氨酸羟化酶（TH）、α-突触核蛋白、胶质纤维酸性蛋白（GFAP）和泛素（Ub）的抗体，对PCA术后1个月和6个月的大鼠以及对照组大鼠的脑组织样本进行免疫组织化学分析。
在对照大鼠中，在黑质致密部（SNc）的神经元细胞体和突起中检测到TH免疫反应性。在纹状体中也可见密集的TH阳性神经元网络。然而，在PCA处理的大鼠中，SNc在1个月和6个月时TH阳性神经元均减少，纹状体中TH阳性纤维也减少。这与SNc中出现α-突触核蛋白免疫反应性神经元同时发生；一些TH阳性神经元也显示出α-突触核蛋白免疫反应性。此外，PCA术后1个月和6个月时，SNc和纹状体中均可见α-突触核蛋白积累，而对照组的黑质纹状体通路中α-突触核蛋白仅轻度表达。PCA术后还可见星形胶质细胞增生，表现为PCA术后1个月至6个月SN和纹状体中GFAP表达增加。在整个PCA暴露过程中，SN中星形胶质细胞的激活水平与TH神经元表达的降低平行。
PCA后α-突触核蛋白的积累可能通过TH的下调以及星形胶质细胞的激活诱导多巴胺能功能障碍。
