Shin Kyungha, Cha Yeseul, Kim Kwang Sei, Choi Ehn-Kyoung, Choi Youngjin, Guo Haiyu, Ban Young-Hwan, Kim Jong-Choon, Park Dongsun, Kim Yun-Bae
College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea.
Behav Neurol. 2016;2016:8521297. doi: 10.1155/2016/8521297. Epub 2016 Mar 21.
Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs) overexpressing choline acetyltransferase (ChAT) improve cognitive function of Alzheimer's disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh) level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA) in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing) time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level.
杏仁核参与恐惧记忆，该记忆可识别预测威胁事件的特定环境线索。杏仁核内神经传递的操纵会影响条件性和非条件性情绪记忆的表达，如恐惧性僵住行为。我们之前证明，过表达胆碱乙酰转移酶（ChAT）的F3.ChAT人神经干细胞（NSCs）通过提高乙酰胆碱（ACh）水平，改善了海马或胆碱能神经损伤的阿尔茨海默病模型大鼠的认知功能。在本研究中，我们研究了F3.ChAT细胞对非条件性恐惧僵住缺陷的影响。在接触猫气味前2周，向大鼠杏仁核注射N-甲基-D-天冬氨酸（NMDA），与正常动物相比，这些大鼠的静息（僵住）时间非常短。NMDA诱导杏仁核神经元变性，导致脑脊液中ACh浓度降低。然而，脑室注射F3.ChAT细胞可在移植后4周减轻杏仁核损伤。在NMDA损伤部位发现了移植的细胞，并产生了ChAT蛋白。此外，根据脑内ACh浓度的恢复情况，接受F3.ChAT细胞的大鼠在远离猫气味源的地方恢复了僵住时间。结果表明，过表达ChAT的人神经干细胞可能通过提高ACh水平促进非条件性恐惧记忆的恢复。
