Hoshi Akihiko, Tsunoda Ayako, Yamamoto Teiji, Tada Mari, Kakita Akiyoshi, Ugawa Yoshikazu
Department of Neurology, Fukushima Medical University, Fukushima, Japan.
Department of Neurology, Fukushima Medical University, Fukushima, Japan.
Neurosci Lett. 2016 Jul 28;626:48-53. doi: 10.1016/j.neulet.2016.05.021. Epub 2016 May 12.
Aquaporin-1 (AQP1) is a water channel expressed in the choroid plexus and participates in forming cerebrospinal fluid. Interestingly, reactive astrocytes also express AQP1 in the central nervous system under some pathological conditions. On the other hand, 3-nitropropionic acid (3NP) is a mitochondrial toxin that causes selective degeneration of striatum; however, its chemical preconditioning is neuroprotective against cerebral ischemia. We previously reported that mild 3NP application is accompanied with numerous reactive astrocytes in rat striatum devoid of typical necrotic lesions. Therefore, we studied whether AQP1 in the rat striatum could be upregulated with reactive astrocytosis using the 3NP model. Immunohistochemical or immunofluorescence analysis showed that reactive astrocytosis in the striatum, which upregulates glial fibrillary acidic protein and glutamine synthetase, was induced by mild doses of 3NP administration. Intriguingly, after 3NP treatment, AQP1 was intensely expressed not only by the subpopulation of astroglia but also by neurons. The AQP1 immunoreactivity became more intensified at the early-subtoxic stage (ES: 24-48h), but not as much in the delayed-subtoxic stage (DS: 96-120h). In contrast, AQP4 expression in the striatum was downregulated after 3NP treatment, in particular during the ES stage. AQP1 upregulation/AQP4 downregulation induced under subtoxic 3NP treatment may play a pivotal role in water homeostasis and cell viability in the striatum.
水通道蛋白-1（AQP1）是一种在脉络丛中表达的水通道，参与脑脊液的形成。有趣的是，在某些病理条件下，反应性星形胶质细胞在中枢神经系统中也表达AQP1。另一方面，3-硝基丙酸（3NP）是一种线粒体毒素，可导致纹状体选择性变性；然而，其化学预处理对脑缺血具有神经保护作用。我们之前报道过，在没有典型坏死病变的大鼠纹状体中，轻度应用3NP会伴随着大量反应性星形胶质细胞。因此，我们使用3NP模型研究了大鼠纹状体中的AQP1是否会随着反应性星形胶质细胞增多而上调。免疫组织化学或免疫荧光分析表明，轻度剂量的3NP给药可诱导纹状体中的反应性星形胶质细胞增多，这会上调胶质纤维酸性蛋白和谷氨酰胺合成酶。有趣的是，3NP处理后，AQP1不仅在星形胶质细胞亚群中强烈表达，在神经元中也强烈表达。AQP1免疫反应性在早期亚中毒阶段（ES：24 - 48小时）变得更强，但在延迟亚中毒阶段（DS：96 - 120小时）则没有那么明显。相比之下，3NP处理后纹状体中AQP4的表达下调，尤其是在ES阶段。亚中毒剂量的3NP处理诱导的AQP1上调/AQP4下调可能在纹状体的水平衡和细胞活力中起关键作用。
