Expression of metabotropic glutamate receptor 5 is increased astrocytes after kainate-induced epileptic seizures

In the CNS there is a differential distribution of the metabotropic glutama te receptor 5 (mGluR5) in neurons and glia. Hippocampal nerve cells contain large amounts of the receptor transcript and protein that are expressed at very law levels in astrocytes. This is unexpected, as mGluR-induced phosph oinositide hydrolysis is substantial in cultured astrocytes and is mediated only by mGluR5 in these cells, In order to detect mGluR5 in astrocytes in vivo, we destroyed in a circumscribed part of the hippocampus nerve cells t hat have high level of receptor expression. Unilateral injection of kainate into the right amygdala produced epileptic seizures, as well as selective degeneration of nerve cells restricted to the ipsilateral CA3 and CA4 regio ns of the hippocampus, followed by the development of gliosis. In the affec ted fields only, mGluR5 immunoreactivity was severely reduced 3 days after kainate injection, followed by a progressive reappearance and lasting prese nce of the receptor protein. Receptor mRNA virtually disappeared from the p yramidal cell layer of the lesioned CA3/4 region. On the other hand, the me ssage level increased persistently in the CA3 stratum lucidum and radiatum, the site of massive astrogliosis. In these sites? mGluR5 mRNA became detec table in double labeling studies in glial fibrillary acidic protein-positiv e astrocytes. We showed previously that growth factors induce a pronounced elevation of mGluR5 expression in cultured astrocytes (Miller et al. J Neur osci 15:6103-6109, 1995). The well-documented increase in the level of grow th factors in the damaged brain may underlie the induction of the receptor expression in astrocytes in vivo, which may also be involved in repair proc esses in the injured nervous tissue. (C) 2000 Wiley-Liss, Inc.