Activated astrocytes in areas of kainate-induced neuronal injury upregulate the expression of the metabotropic glutamate receptors 2/3 and 5

Abstract.

All forms of brain injury induce activation of astrocytes, although different types of injury induce different astrocytic responses. Activated astrocytes are characterised by hypertrophy, proliferation and increased expression of glial fibrillary acidic protein (GFAP). However, neither the process by which astrocytes become reactive nor the consequences are well understood. Recently, the application of specific growth factors to primary astrocytic cultures was shown to regulate dramatically the level of expression of the metabotropic glutamate receptors (mGluR) 5 and 3. In the present study, we have used an intracerebroventricular injection of a subconvulsive dose of kainic acid to produce a lesion of CA3a pyramidal neurones in the mouse hippocampus and to investigate whether mGluR expression was altered in reactive astrocytes in vivo. Immunohistochemical analysis showed strong mGluR5 and mGluR2/3 immunoreactivity in glial cells within the area of neuronal loss possessing the morphological feature of activated astrocytes. Double labelling with GFAP confirmed the expression of mGluRs by reactive astrocytes. The mechanical injury produced by the needle insertion in the cerebral cortex also produced enhanced expression of mGluR5 and mGluR2/3 in activated astrocytes proximal to the area of neuronal injury. Our finding of an increased mGluR expression in reactive astrocytes in vivo suggests that transcriptional regulation by specific growth factors on mGluRs is a phenomenon extendible to specific circumstances in vivo and not limited to in vitro models. Identification of the mechanisms of this adaptive plasticity will be central in the understanding of the events leading to neuronal survival and/or death.