Article

Carnosine suppresses oxygen-glucose deprivation/ recovery-induced proliferation and migration of reactive astrocytes of rats in vitro

Authors: Li OU-YANG1, Yuan LIU1, Bing-yu WANG1, Pei CAO1, Jing-jing ZHANG1, Yu-yan HUANG1, Yao SHEN1, Jian-xin LYU1,2
1 Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life sciences, Wenzhou Medical University, Wenzhou 325035, China
2 Laboratory Medicine College, Hangzhou Medical College, Hangzhou 310053, China
Correspondence to: Yao SHEN: yueshen-2002@163.com,
DOI: 10.1038/aps.2017.126
Received: 24 February 2017
Accepted: 5 June 2017
Advance online: 21 September 2017

Abstract

Abstract
Glial scar formation resulted from excessive astrogliosis limits axonal regeneration and impairs recovery of function, thus an intervention to ameliorate excessive astrogliosis is crucial for the recovery of neurological function after cerebral ischemia. In this study we investigated the effects of carnosine, an endogenous water-soluble dipeptide (β-alanyl-L-histidine), on astrogliosis of cells exposed to oxygen-glucose deprivation/recovery (OGD/R) in vitro. Primary cultured rat astrocytes exhibited a significant increase in proliferation at 24 h recovery after OGD for 2 h. Pretreatment with carnosine (5 mmol/L) caused G1 arrest of reactive astrocytes, significantly attenuated OGD/R-induced increase in cyclin D1 protein expression and suppressed OGD/R-induced proliferation of reactive astrocytes. Carnosine treatment also reversed glycolysis and ATP production, which was elevated at 24 h recovery after OGD. A marked increase in migration of reactive astrocytes was observed at 24 h after OGD, whereas carnosine treatment reversed the expression levels of MMP-9 and suppressed the migration of astrocytes. Furthermore, carnosine also improved neurite growth of cortical neurons co-cultured with astrocytes under ischemic conditions. These results demonstrate that carnosine may be a promising candidate for inhibiting astrogliosis and promoting neurological function recovery after ischemic stroke.
Keywords: cerebral ischemia; astrogliosis; carnosine; oxygen-glucose deprivation/recovery (OGD/R); cell cycle; energy metabolism; neurite growth

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