title: Metabotropic glutamate receptor 5 (mGluR5) regulates proliferation and differentiation of neuronal progenitors in the developmental hippocampus.
abstract: Metabotropic glutamate receptor 5 (mGluR5) is involved in neural stem cell self-renewal, proliferation, differentiation and survival. In this study, we aimed to further determine the role of mGluR5 in the development of hippocampus using mGluR5 deficit (mGluR5(-/-)) and wild type (mGluR5(+/+)) mice at different developmental ages. We showed that the number of BrdU, NeuroD and DCX immunopositive cells was reduced significantly in mGluR5(-/-) than in mGluR5(+/+) mice from postnatal 7 days (P7) to P28, but not at P60. The length and intensity of DCX immunopositive apical dendrites in the dentate gyrus of mGluR5(-/-) mice were much shorter and lower than in mGluR5(+/+) mice respectively at P14, P21 and P28. NeuN immunostaining indicated an accelerated maturation of hippocampal neurons in mGluR5(-/-) mice. When mGluR5(+/+) mice were treated with 2-methyl-6-(phenylethynyl) pyridine (MPEP), a selective antagonist of mGluR5, decreased proliferation of progenitor cells was observed in the hippocampus at early postnatal developmental stages. At P14, there were more BrdU(+) cells in the stratum granulosum and subgranular layer of the dentate gyrus in mGluR5(+/+) than in mGluR5(-/-) mice, but the percentage of BrdU(+)+NeuroD(+)/BrdU(+) in the dentate gyrus did not change significantly between the two genotypes of mice. Western Blot study suggested that programmed neuronal death was p53-dependent apoptosis in the developmental hippocampus in mGluR5(+/+) mice.
authors.affiliation: Institute of Neurobiology, Department of Anatomy and Embryology, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Xin Li
authors.initials: XL
authors.lastname: Xiao
authors.forename: Dong Liang
authors.initials: DL
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Feng-Ru
authors.initials: FR
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003712:Dendrites / Q000502:physiology; D000089662:Doublecortin Protein; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine