Involvement of interferon-gamma and its receptor in the activation of astrocytes in the mouse hippocampus following entorhinal deafferentation.

The activation of glial cells has been thought to be a universal and important reaction to trauma and pathology in the mammalian central nervous system. The mechanism of glial activation is not completely clear to date, but numerous cytokines have been demonstrated to effectively influence the process in vitro and in vivo. Here we reported the axotomy-induced upregulation of interferon-gamma (IFN-gamma) receptor mRNA in the mouse hippocampus following transections of the entorhinal afferents. Northern blot analysis showed that the transcripts of IFN-gamma receptor were upregulated in a transient manner in the deafferented mouse hippocampus. In situ hybridization confirmed the temporal upregulation of IFN-gamma receptor mRNA specifically in the denervated areas of the mouse hippocampus, which showed that the expression of IFN-gamma receptor mRNA rose slightly at 2 days postlesion, increased remarkably at 3 days postlesion, nearly reached the maximum at 7 days postlesion, and almost returned to control levels at 15 days postlesion. Double labeling further proved that the upregulated IFN-gamma receptor mRNA was confined to reactive astrocytes. At 2 and 3 days postlesion, we also observed the expression of IFN-gamma mRNA by a small number of cells in the denervated areas. We noted that the upregulation of both IFN-gamma and its receptor expression coincided spatiotemporally with astroglial activation, suggesting the potential involvement of IFN-gamma and its receptor in the activation process of astrocytes in the hippocampus following entorhinal deafferentation. 2004 Wiley-Liss, Inc.