The developmental expression of metabotropic glutamate receptor 4 in prenatal human frontal lobe and neurogenesis regions

Metabotropic glutamate receptors, besides ionotropic receptors, mediate the complicated effect of glutamate on neurogenesis. Previous studies showed that metabotropic glutamate receptor 4 (mGluR4) regulated the proliferation and differentiation of neural stem/progenitor cells in vitro. However, little is known about the expression pattern of mGluR4 on prenatal central nervous system in vivo, especially the human being.

The normal brain tissues of human fetus were collected and divided into 4 groups according to the gestational age: 9-11 W, 14-16 W, 22-24 W and 32-36 W. Then the expression of mGluR4 was evaluated at mRNA and protein levels by means of PCR or immunohistochemistry method, respectively. The type of cell expressing mGluR4 was further investigated using double-labeling immunofluorescence.

RT-PCR showed that the mRNA of mGluR4 could be detected in frontal lobe from 9 W to 32 W and real-time PCR quantificationally demonstrated the mRNA increased with development. Similarly, immnoreactivity was found in all layers of frontal lobe, VZ/SVZ. The intensity scores analysis showed that the staining became stronger and the range extended gradually with development. The double-labeling immunofluorescence showed that mGluR4 was present in neural stem/progenitor cells (nestin-positive cells after 9 W), young neurons (DCX-positive cells after 9 W), mature neurons (NeuN-positive cells in cortex after 32 W), as well as typical astrocytes (GFAP-positive cells in medulla after 32 W).

These results supply an important evidence that mGluR4 is expressed in prenatal human cerebrum, and main kinds of cells related to neurogenesis are involved in its expression.