EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

International Journal of Molecular Sciences

Bo Young Choi²  Jin Hee Kim²  Hyun Jung Kim²  Bo Eun Lee²  In Yeol Kim²  Min Sohn¹  Sang Won Suh² 

[1] Department of Nursing, Inha University, Incheon 402-751, Korea; E-Mail:;Department of Physiology, Hallym University, College of Medicine, Chuncheon 200-702, Korea; E-Mails:

关键词: EAAC1;    cysteine;    blood–brain barrier;    ischemia;    glutathione;    vessel disorganization;   

DOI  :  10.3390/ijms151119444

来源: mdpi

【 摘 要 】

EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1^−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB) disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1^−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.