Mechanism of cerebellar neuronal cell death in CTX patients

CTX是一种遗传性脂质储存疾病，以高胆固醇血症、小脑性共济失调、跟腱黄瘤、白内障和过早动脉粥样硬化为特征。小脑性共济失调和白内障的病因尚不清楚。为了阐明小脑性共济失调和白内障的病因，我们建立了CTX模型大鼠，喂食含胆固醇的饲料。经组织化学分析，胆固醇沉积于晶状体、角膜和小脑。因此，我们假设胆固醇可能诱导小脑神经元细胞凋亡，包括浦肯野细胞、角膜内皮细胞和晶状体上皮细胞。对这些细胞进行原代培养，并在培养基中加入胆固醇。TUNEL法、半胱天冬酶（caspase）的诱导及细胞形态学变化均表明胆固醇可诱导这些细胞凋亡。本研究结果可能解释CTX患者小脑性共济失调和白内障的发病机制。

CTX is a hereditary lipid storage disease characterized by hypercholestanolemia, cerebellar ataxia, Achilles tendon xanthoma, cataract, and premature atherosclerosis. The etiology of cerebellar ataxia and cataract is unknown. To clarify the etiology of cerebellar ataxia and cataract, we established model rats for CTX fed diets containing cholestanol. By histochemical analysis cholestanol was deposited in lens, cornea, and cerebellum. Therefore, we hypothesized that cholestanol may induce apoptosis of cerebellar neuronal cells including Purkinje cells, corneal endothelial cells, and lens epithelial cells. Primary culture of these cells were performed and cholestanol was added into culture media. Cholestanol induced apoptosis of these cells as judged by TUNEL method, induction of caspases, and morphological changes of these cells. The results in the present study may explain the mechanism of cerebellar ataxia and cataract in CTX patients.