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. © 2012 Elsevier B.V.