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

All forms of brain injury induce activation of astrocytes, although differe nt types of injury induce different astrocytic responses. Activated astrocy tes are characterised by hypertrophy, proliferation and increased expressio n of glial fibrillary acidic protein (GFAP). However, neither the process b y which astrocytes become reactive nor the consequences are well understood . Recently, the application of specific growth factors to primary astrocyti c cultures was shown to regulate dramatically the level of expression of th e metabotropic glutamate receptors (mGluR) 5 and 3. In the present study, w e have used an intracerebroventricular injection of a subconvulsive dose of kainic acid to produce a lesion of CA3a pyramidal neurones in the mouse hi ppocampus and to investigate whether mGluR expression was altered in reacti ve astrocytes in vivo. Immunohistochemical analysis showed strong mGluR5 an d mGluR2/3 immunoreactivity in glial cells within the area of neuronal loss possessing the morphological feature of activated astrocytes. Double label ling with GFAP confirmed the expression of mGluRs by reactive astrocytes. T he mechanical injury produced by the needle insertion in the cerebral corte x also produced enhanced expression of mGluR5 and mGluR2/3 in activated ast rocytes proximal to the area of neuronal injury. Our finding of an increase d mGluR expression in reactive astrocytes in vivo suggests that transcripti onal regulation by specific growth factors on mGluRs is a phenomenon extend ible to specific circumstances in vivo and not limited to in vitro models. Identification of the mechanisms of this adaptive plasticity will be centra l in the understanding of the events leading to neuronal survival and/or de ath.