Piao Wenying, Nishina Kazutaka, Yoshida-Tanaka Kie, Kuwahara Hiroya, Nishina Tomoko, Sakata Mina, Mizusawa Hidehiro, Yokota Takanori
Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
J Med Dent Sci. 2013 Mar 1;60(1):9-16.
The choroid plexus (CP) is present on the ventricular walls of the brain, produces cerebrospinal fluid (CSF), contains many blood vessels, and is a major functional component of the blood-CSF barrier. The CP is an important site in the pathophysiology of various neurological diseases, including Alzheimer's disease and meningeal amyloidosis. We performed gene silencing in the CP in vivo by using an antisense oligonucleotide (ASO). A short ASO of length 12 nucleotides was intravenously injected into rats. The ASO was not delivered to neurons or glia in the central nervous system, but was successfully delivered into the CP, and resulted in a significant reduction of endogenous target gene expression in epithelial cells within the CP. Although the mechanism of uptake of the ASO by the CP was not elucidated, the ASO bound to albumin in vivo, and the distribution of ASO delivery was similar to that of albumin delivery. These findings suggest that we inhibited target gene expression in the epithelial cells of the CP via albumin-ASO conjugates. This strategy should be useful for investigations of the function of CP, and for the development of new gene-silencing therapies for diseases with pathophysiology related to the CP.
脉络丛（CP）位于脑室内壁，产生脑脊液（CSF），含有许多血管，是血脑屏障的主要功能成分。CP是包括阿尔茨海默病和脑膜淀粉样变性在内的各种神经疾病病理生理学中的一个重要部位。我们通过使用反义寡核苷酸（ASO）在体内对CP进行基因沉默。将长度为12个核苷酸的短ASO静脉注射到大鼠体内。该ASO未递送至中枢神经系统中的神经元或神经胶质细胞，但成功递送至CP，并导致CP内上皮细胞中内源性靶基因表达显著降低。尽管未阐明CP摄取ASO的机制，但ASO在体内与白蛋白结合，且ASO递送的分布与白蛋白递送的分布相似。这些发现表明，我们通过白蛋白-ASO偶联物抑制了CP上皮细胞中的靶基因表达。该策略对于研究CP的功能以及开发与CP病理生理学相关疾病的新基因沉默疗法应该是有用的。
