Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow MSCs on promoting alveolarization in bronchopulmonary dysplasia.

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow MSCs on promoting alveolarization in bronchopulmonary dysplasia. Am J Physiol Cell Physiol. 2019 Mar 27;: Authors: Yue Y, Luo Z, Liao Z, Zhang L, Liu S, Wang M, Zhao F, Cao C, Ding Y, Yue S Abstract We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments we confirmed that intrauterine hypoxia also impaired bone marrow MSCs proliferation and decreased cell cycling activity. In vitro, using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-D-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When using MK-801 or memantine as NMDAR antagonists in vitro or in vivo, the reduction of cell cycling activity and the proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased the c...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research