Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Cognitive Function of Kainic Acid-Induced Learning and Memory Deficit Animals

Cell Transplantation

Brief Communication

Dongsun Park¹  Tae Kyun Kim¹  Hyomin Kang¹  Sun Hee Lee¹  Yun-Bae Kim²  Inja Lim³  Seong Soo Joo⁴  Seung U. Kim⁵  Hong Jun Lee⁵  Akinori Matsuo⁶  Ikuo Tooyama⁶ 

[1] College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea;College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea;Division of Neurology, Department of Medicine, University of British Columbia Hospital, Vancouver, Canada;Department of Physiology, Chung-Ang University Medical School, Seoul, Republic of Korea;Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, Republic of Korea;Medical Research Institute, Chung-Ang University Medical School, Seoul, Republic of Korea;Division of Neurology, Department of Medicine, University of British Columbia Hospital, Vancouver, Canada;Molecular Neuroscience Research Center, Shiga University of Medical Science, Ohtsu, Japan;

关键词: Learning and memory;    Alzheimer disease;    Kainic acid;    Neural stem cells;    Choline acetyltransferase (ChAT) gene;    Acetylcholine;   

DOI  :  10.3727/096368911X586765

 received in 2011-01-12, accepted in 2011-03-31,  发布年份 2012

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

Unknown   
© 2012 Cognizant Comm. Corp.

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