Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury

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 demonstrat...

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Main Authors: Kyungha Shin, Yeseul Cha, Kwang Sei Kim, Ehn-Kyoung Choi, Youngjin Choi, Haiyu Guo, Young-Hwan Ban, Jong-Choon Kim, Dongsun Park, Yun-Bae Kim
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Behavioural Neurology
Online Access:http://dx.doi.org/10.1155/2016/8521297
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author Kyungha Shin
Yeseul Cha
Kwang Sei Kim
Ehn-Kyoung Choi
Youngjin Choi
Haiyu Guo
Young-Hwan Ban
Jong-Choon Kim
Dongsun Park
Yun-Bae Kim
author_facet Kyungha Shin
Yeseul Cha
Kwang Sei Kim
Ehn-Kyoung Choi
Youngjin Choi
Haiyu Guo
Young-Hwan Ban
Jong-Choon Kim
Dongsun Park
Yun-Bae Kim
author_sort Kyungha Shin
collection DOAJ
description 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.
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spelling doaj-art-386e0cfabbe848c09748d0a0d0a35cd72025-08-20T02:38:58ZengWileyBehavioural Neurology0953-41801875-85842016-01-01201610.1155/2016/85212978521297Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala InjuryKyungha Shin0Yeseul Cha1Kwang Sei Kim2Ehn-Kyoung Choi3Youngjin Choi4Haiyu Guo5Young-Hwan Ban6Jong-Choon Kim7Dongsun Park8Yun-Bae Kim9College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaAmygdala 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.http://dx.doi.org/10.1155/2016/8521297
spellingShingle Kyungha Shin
Yeseul Cha
Kwang Sei Kim
Ehn-Kyoung Choi
Youngjin Choi
Haiyu Guo
Young-Hwan Ban
Jong-Choon Kim
Dongsun Park
Yun-Bae Kim
Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury
Behavioural Neurology
title Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury
title_full Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury
title_fullStr Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury
title_full_unstemmed Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury
title_short Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury
title_sort human neural stem cells overexpressing choline acetyltransferase restore unconditioned fear in rats with amygdala injury
url http://dx.doi.org/10.1155/2016/8521297
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