title: Protective Effect of Minocycline Against Ketamine-Induced Injury in Neural Stem Cell: Involvement of PI3K/Akt and Gsk-3 Beta Pathway.
abstract: It has been suggested that ketamine cause injury during developing brain. Minocycline (MC) could prevent neuronal cell death through the activation of cell survival signals and the inhibition of apoptotic signals in models of neurodegenerative diseases. Here we investigated the protective effect of MC against ketamine-induced injury in neural stem cells (NSCs) from neonatal rat. Ketamine (100 μM/L) significantly inhibited NSC proliferation, promoted their differentiation into astrocytes and suppressed neuronal differentiation of NSCs. Moreover, the apoptotic level was increased following ketamine exposure. MC pretreatment greatly enhanced cell viability, decreased caspase-3-like activity, even reversed the differentiation changes caused by ketamine. To elucidate a possible mechanism of MC' neuroprotective effect, we investigated the phosphatidylinositol 3-kinase (PI3K) pathway using LY294002, a specific PI3K inhibitor. Immunoblotting revealed that MC enhanced the phosphorylation/activation of Akt and phosphorylation/inactivation of glycogen synthase kinase-3beta (Gsk-3β). Our results suggest that PI3K/Akt and Gsk-3β pathway are involved in the neuroprotective effect of MC.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Weisong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Giri
authors.affiliation: Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University Xi'an, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Lu
authors.affiliation: Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University Xi'an, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, University of Virginia Charlottesville, VA, USA.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University Xi'an, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhang
keywords: Akt; Gsk-3β; caspase-3; ketamine; minocycline; neural stem cells; neuroprotective effect