AMN082 promotes the proliferation and differentiation of neural progenitor cells with influence on phosphorylation of MAPK signaling pathways.
Metabotropic glutamate receptors (mGluRs) are expressed in neural progenitor cells (NPCs) and may play important roles in the neurogenesis during embryonic development and adult brain repair following injuries. In the present study, we investigated the expression of metabotropic glutamate receptor 7 (mGluR7) and the possible roles of this receptor in the proliferation and differentiation of NPCs isolated from embryonic Sprague-Dawley (SD) rats. The results showed that under the normal culture and the hypoxic condition, both mRNA and protein of mGluR 7 are expressed in NPCs. Administration of AMN082, a selective agonist ofmGluR7, promoted the proliferation and differentiation of NPCs. We also demonstrated that activation of JNK and ERK signaling pathways are involved in the differentiation of NPCs into neurons following AMN082 treatment. AMN082 stimulated p-ERK and p-JNK2 expression in both normal and hypoxic conditions at different time points. But p-p38 decreased in normoxia and increased in hypoxia condition at 6h following treated with AMN082 activation. In conclusion, mGluR7 possesses the potential in promoting rat NPCs proliferation and differentiation in vitro with changes in phosphorylation of mitogen-activated protein kinases (MAPK) signaling pathways, suggesting that mGluR7 may exert an important role in brain development and repair of the central nervous system after injury.
Tian
Yumei
Y
Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Education Ministry, The State Key Subject for Physiology, Xi'an Jiaotong University College of Medicine, China.
Liu
Yong
Y
Chen
Xinlin
X
Kang
Qianyan
Q
Zhang
Junfeng
J
Shi
Qindong
Q
Zhang
Haixia
H
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001559:Benzhydryl Compounds; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D048049:Extracellular Signal-Regulated MAP Kinases