REGION-SPECIFIC ACTIVATION OF MICROGLIAL CELLS IN THE RAT SEPTAL COMPLEX FOLLOWING FIMBRIA-FORNIX TRANSECTION

Studies of postlesional microglial activation may gain insight into mi croglia/neuronal interactions in processes of neurodegeneration. We co mpared the microglial response after axotomy of septohippocampal proje ction neurons with that seen after selective immunolesioning of cholin ergic septohippocampal neurons with the immunotoxin 192 IgG-saporin. U sing the microglial marker isolectin B-4 from Griffonia simplicifolia (GSA I-B-4), we found striking differences in the microglial response between these two lesion paradigms. Following axotomy of septohippocam pal neurons by fimbria-fornix transection (ff-t), there was only a mod erate and short-lasting microglial reaction in the medial septum (MS) in the early postlesion period. Prelabeling of septohippocampal neuron s with Fluoro-Gold (FG prior to axotomy revealed the survival of most neurons, and only very rarely were microglial cells observed that had phagocytosed FG-labeled debris. In the lateral septum (LS) containing the degenerating terminals of hippocamposeptal fibers transected by ff -t, a heavy reaction of lectin-labeled activated microglial cells asso ciated with high phagocytotic activity was noticed. Unexpectedly, afte r a long survival time (6 months) following ff-t, we observed an incre ase in microglial GSA I-B-4 labeling in the MS. In contrast, an invers e pattern of the microglial response, i.e., a strong initial reaction in the MS and very little microglial activation in the LS, was observe d after immunolesioning. Our results indicate that the microglial reac tion in the MS following ff-t differs substantially from that seen in other models of axotomy. (C) 1998 Wiley-Liss, Inc.