摘要
为了研究本实验室筛选出的单体化合物EUK4010对Presenilin-1/Presenilin-2双基因敲除小鼠神经退行性症状的作用及机制,将EUK4010(10μg/g体重)分别作用于2月龄和6月龄的双基因敲除小鼠(dKO小鼠),通过组织学、实时荧光定量PCR及Western blot、行为学等方法发现该化合物对dKO小鼠的体重下降、脑室扩大、海马萎缩等有一定缓解作用,但对dKO小鼠认知行为的改变尚不明显.进一步分析发现,EUK4010对dKO小鼠神经退行性症状的改善可能是抑制了由Presenilin-1/Presenilin-2双基因敲除导致的GFAP、C1qα与C4等炎症反应相关基因在皮层与海马中的表达上调所致.
To investigate the effects of EUK4010 on the neurodegenerative phenotypes of Presenilin-1/Presenilin-2 double knockout mice,10μg/g of body weight of EUK4010 was administrated on Presenilin-1/Presenilin-2 double knockout mice at 2-7 months and 6-11 months,respectively.Through the tests of morphology,Real-time PCR and behavior,it is found that the neurodegenerative symptoms of loss of body weight,enlargement of ventricles and atrophy of hippocampus were ameliorated by EUK4010,whereas the cognitive behaviors were not significantly influenced by EUK4010.Further investigations indicated that the ameliorations of the neurodegenerative symptoms by EUK4010 could depend on down-regulating the up-regulation of inflammatory response mediators such as GFAP,C1qα and C4 gene in dKO cortex and hippocampus induced by Presenilin-1/Presenilin-2 double knockout.
出处
《复旦学报（自然科学版）》
CAS
CSCD
北大核心
2009年第5期648-655,共8页
Journal of Fudan University：Natural Science
基金
上海市科学技术委员会"登山行动计划"资助项目(06DZ19003)
