ABSTRACT
The aim of the present work was to perform, by in situ hybridization, a time-course analysis of the glial cell line-derived neurotrophic factor (GDNF) and its receptor mRNA expression in two models of brain injury in the rat: (a) excitotoxic lesion by ibotenic acid injection in the hippocampal formation; (b) mechanical lesion by needle insertion through the cerebral cortex including the white matter of the corpus callosum. The time-course analysis, ranging from 6h to 8 days, showed that the GDNF and its receptor (RET, GFRalpha-1 and GFRalpha-2) mRNA expressions were differentially up-regulated in both models of lesion. This in vivo regulation of the GDNF and its receptor mRNA expression indicates their involvement in the process of neuronal protection and regeneration occurring after brain injury.
Subject(s)
Brain Injuries/metabolism , Brain Injuries/physiopathology , Gene Expression Regulation/physiology , Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Animals , Autoradiography/methods , Brain Injuries/chemically induced , Glial Cell Line-Derived Neurotrophic Factor/genetics , Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics , Ibotenic Acid , Male , RNA, Messenger/metabolism , Rats , Rats, Wistar , Time FactorsABSTRACT
In order to understand the role of metabotropic glutamate receptors (mGluRs) in the brain, it is important to know how the mGluRs are differentially expressed among the different cell types. At present, the cellular expression of mGluR3 and mGluR5 has been mostly studied in terms of proteins with observations suggesting the expression of both mGluR3 and mGluR5 in neuronal and in glial cells. In order to verify the brain cell type-expressing mGluR3 and mGluR5 mRNAs, both in normal and injured brain, we performed a double labeling analysis, by in situ hybridization for mGluR3 or mGluR5 mRNA and immunohistochemistry for specific cellular markers. This approach allowed us to find mGluR3 mRNA expressed in neurons (NeuN-positive cells), and in glial cells, such as astrocytes (GFAP-positive cells) and oligodendrocytes (CNPase-positive cells). The same analysis showed that only NeuN-positive cells express mGluR5 mRNA. The time course of mGluR3 mRNA expression in two models of hippocampal formation lesion, kainate-induced seizures or ibotenic acid injection, showed an increased expression of mGluR3 in the area of lesion. This effect appears 1 week after the injury and was localized in GFAP- and CNPase-positive cells. In contrast, mGluR5 was not found expressed in the area of lesion. The present results contribute to extend available data on cell type-expressing mGluR3 and mGluR5 in normal and injured brain and could be relevant to understand the mechanisms that drive neuron-glial cells interaction both in normal and repairing processes.
