Protective effects of N-acetyl-L-cysteine in human oligodendrocyte progenitor cells and restoration of motor function in neonatal rats with hypoxic-ischemic encephalopathy.
Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects of N-acetyl-l-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea ; Ajou University School of Medicine, Suwon, Gyeonggi 443-380, Republic of Korea.
Dongsun
D
Park
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
Kyungha
K
Shin
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
Ehn-Kyoung
EK
Choi
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
Youngjin
Y
Choi
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
Ja-Young
JY
Jang
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
Jihyun
J
Kim
Department of Food Science and Technology, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea.
Heon-Sang
HS
Jeong
Department of Pediatrics, Soonchunhyang University Hospital, Seoul 140-743, Republic of Korea.
Wooryoung
W
Lee
Central Research Institute, Dr. Chung's Food Co. Ltd., Cheongju, Chungbuk 361-782, Republic of Korea.
Yoon-Bok
YB
Lee
Division of Neurology, University of British Columbia Hospital, Vancouver, BC, Canada V6T 2B5.
Seung Up
SU
Kim
Department of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, Gangwon 210-702, Republic of Korea.
Seong Soo
SS
Joo
College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 362-763, Republic of Korea ; Division of Neurology, University of British Columbia Hospital, Vancouver, BC, Canada V6T 2B5.
Yun-Bae
YB
Kim