Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Cognitive Function of Kainic Acid-Induced Learning and Memory Deficit Animals
Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Cognitive Function of Kainic Acid-Induced Learning and Memory Deficit Animals
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DOI：
10.3727/096368911x586765
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Kim, Seung U.
中科院分区：
文献类型：
--
作者：
Park, Dongsun;Joo, Seong Soo;Kim, Seung U.
阿尔茨海默病（Alzheimer disease，AD）是一种以记忆和认知功能丧失为特征的进行性神经退行性疾病。在AD患者中，胆碱能系统的功能障碍是认知障碍的主要原因，并且观察到胆碱乙酰转移酶（ChAT）（一种负责乙酰胆碱（ACh）合成的酶）的活性降低。本研究探讨了经ChAT基因修饰的人神经干细胞（NSCs）脑移植是否能改善红藻氨酸（KA）诱导的学习障碍大鼠的认知功能。海马CA3区注射KA可引起严重的神经元丢失，导致严重的学习记忆障碍。F3.ChAT人神经干细胞侧脑室移植可明显改善KA所致学习障碍动物的学习记忆功能，并可提高脑脊液中ACh水平。F3.ChAT人神经干细胞迁移到KA诱导的损伤部位（CA3）并分化为神经元和星形胶质细胞。本研究表明，表达ChAT的人神经干细胞具有损伤向性，可通过提高ACh水平改善海马损伤后学习障碍模型大鼠的认知功能。
Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT), an enzyme responsible for acetylcholine (ACh) synthesis, is observed. In the present study we investigated if brain transplantation of human neural stem cells (NSCs) genetically modified to encode ChAT gene improves cognitive function of kainic acid (KA)-induced learning deficit rats. Intrahippocampal injection of KA to hippocampal CA3 region caused severe neuronal loss, resulting in profound learning and memory deficit. F3.ChAT human NSCs transplanted intracerebroventricularly improved fully the learning and memory function of KA-induced learning deficit animals, in parallel with the elevation of ACh levels in cerebrospinal fluid. F3.ChAT human NSCs migrated to the KA-induced injury site (CA3) and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs expressing ChAT have lesion-tropic property and improve cognitive function of learning deficit model rats with hippocampal injury by increasing ACh level.