Abstract：
:Melatonin is a hormone that mostly produced from the pineal gland, and it performs as a strong neuroprotectant to both neuron and glial cells against methamphetamine (METH)-induced neurotoxicity. Recently, it has been found that METH also damages the blood brain barrier (BBB) structure and function. However, the protective mechanism of melatonin on the BBB impairment caused by METH has not been investigated. In this study, the primary rat brain microvascular endothelium cells (BMVECs) isolated from neonatal rats was used to investigate the protective effect of melatonin on METH-induced BBB impairment and the underlying mechanism. The results demonstrated that melatonin decreased the level of reactive oxygen species (ROS), reactive nitrogen species (RNS), and apoptosis induced by METH via NADPH oxidase (NOX)-2 since apocynin, a NOX-2 inhibitor abolished those changes. In addition, melatonin was found to improve cell integrity by increasing the transendothelial electric resistance (TEER) values, and up-regulate the tight junction proteins ZO-1, occludin, and claudin-5, thereby decreasing the paracellular permeability caused by METH mediated by NOX-2. Our data suggest that METH induces BBB impairment by mediating NOX-2 activity, and then induces oxidative and nitrative stress, as well as apoptosis, which causes the impairment of cell integrity, and that melatonin reduces these negative effects of METH by mediating via MT1/2 receptors.
journal_name
Brain Resjournal_title
Brain researchauthors
Jumnongprakhon P,Govitrapong P,Tocharus C,Tocharus Jdoi
10.1016/j.brainres.2016.08.045subject
Has Abstractpub_date
2016-11-01 00:00:00pages
84-92eissn
0006-8993issn
1872-6240pii
S0006-8993(16)30605-9journal_volume
1650pub_type
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