title: mGluR5 promotes the differentiation of rat neural progenitor cells into cholinergic neurons and activation of extracellular signal-related protein kinases.
abstract: Metabotropic glutamate receptors (mGluRs) regulate neurogenesis in the mammalian central nervous system during development and throughout adulthood. However, the mechanisms remain unknown. The present study was aimed at investigating the effect of mGluR5 on the differentiation of rat neural progenitor cells (NPCs) into neurons as well as the underlying molecular mechanisms. NPCs were treated with mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR5 siRNA, and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MPEP), respectively. Three different subtypes of neurons (cholinergic, GABAergic, and dopaminergic neurons) were evaluated, and the activation of signaling pathways of mitogen-activated protein kinases was determined. Results showed that CHPG caused rat NPCs to differentiate into neurons, whereas mGluR5 siRNA and MPEP inhibited the cell differentiation. The proportion of cholinergic neurons increased with CHPG treatment and decreased after siRNA or MPEP treatment, whereas there were no significant changes in the proportions of GABAergic and dopaminergic neurons after treatment. The phosphorylated ERK1/2 levels increased after CHPG treatment and decreased after siRNA or MPEP treatment. In conclusion, our findings showed that mGluR5 caused rat NPCs to differentiate into cholinergic neurons by activating ERKs, suggesting that mGluR5 may play a significant role in the mechanism and treatment of degenerative diseases such as Alzheimer's disease.
authors.affiliation: aInstitute of Neurobiology bDepartment of Genetics and Cell Biology, Environment and Genes Related to Diseases Key Laboratory of Education Ministry, Xi'an Jiaotong University College of Medicine cDepartment of Anatomy, Xi'an Medical University, Xi'an, People's Republic of China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zhao
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiao
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Ni
authors.initials: N
authors.lastname: Hou
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.forename: Jianshui
authors.initials: J
authors.lastname: Zhang
authors.forename: Pengbo
authors.initials: P
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Xu
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D059329:Cholinergic Neurons / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D059330:GABAergic Neurons / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D010648:Phenylacetates / Q000494:pharmacology*; D010766:Phosphorylation / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D010648:Phenylacetates; D011725:Pyridines; D034741:RNA, Small Interfering; D064529:Receptor, Metabotropic Glutamate 5; C121465:6-methyl-2-(phenylethynyl)pyridine; D048049:Extracellular Signal-Regulated MAP Kinases; D005998:Glycine