Effects of the group II mGlu receptor agonist 2R,4R-APDC on dentate gyrus cell proliferation in the adult rat brain after diffuse brain injury

Neurol Res. 2011 May;33(4):381-8. doi: 10.1179/016164110X12816242542733.


Objectives: Diffuse brain injury (DBI) has been shown to increase the proliferation of granule cell precursors in the adult dentate gyrus (DG). However, the mechanism by which DBI-induced cell proliferation in the DG may enhance seizure susceptibility remains largely unknown.

Materials and methods: Using bromodeoxyuridine (BrdU) immunohistochemistry, we examined the effects of group II metabotropic glutamate receptor (mGluR) agonist, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), on cell proliferation in the DG after DBI.

Results: It has been found that 2R,4R-APDC significantly blocked DBI-induced increase in the number of BrdU-positive cells in the DG, especially in hilus. In addition, double-label immunofluorescence staining showed that treatment with APDC did not affect the differentiation of newborn cells into neurons or astrocytes. Taken together, our findings indicate that the activation of mGluR system may inhibit the DBI-induced cell proliferation in the DG, but not the differentiation of newborn cells.

Discussion: It is suggested that 2R,4R-APDC has potential neuroprotection via inhibiting the aberrant neurogenesis induced by DBI, which is an important pathological basis of seizure or other abnormalities following DBI.

MeSH terms

  • Animals
  • Brain Injuries / drug therapy*
  • Brain Injuries / mortality
  • Brain Injuries / pathology*
  • Cell Proliferation / drug effects*
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / metabolism
  • Dentate Gyrus / pathology
  • Disease Models, Animal
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Agonists / therapeutic use
  • Male
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Neurogenesis / drug effects
  • Neurogenesis / physiology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Proline / analogs & derivatives*
  • Proline / pharmacology
  • Proline / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / physiology


  • 4-aminopyrrolidine-2,4-dicarboxylic acid
  • Excitatory Amino Acid Agonists
  • Neuroprotective Agents
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Proline