Study On Glial Activation

Transections of entorhinal afferents lead to anterograde degeneration ofperforant path fibers in their main hippocampal termination zones. In response toneural degeneration, dramatic activation of glial cells as demonstrated by rapidchange in cell morphology, increased activity of migration and proliferation, activephagocytosis as well as secretion of cytokines, takes place in the denervated zonesof the hippocampus. The enhanced motility of activated glial cells is dependent onprompt actin-cytoskeleton reorganization in which actin-binding proteins havebeen demonstrated as crucial regulators. In the present studies, we reported theexpression of three actin-binding proteins profilin, gelsolin and thymosin β4 (Tβ4)in the murine hippocampus following entorhinal denervation. Northern blotanalysis showed that the transcripts of three genes remarkably increased as earlyas 1 day post-lesion (dpl), reached maximal levels at 3dpl and almost returned tothe control levels by 2 weeks post-lesion. In situ hybridization confirmed thetemporal upregulation of the genes in the deafferented zones of the mousehippocampus. The immunohistochemistry exhibited the transient upregulation ofgelsolin protein in the deafferented hippocampus with the time course consistentwith that of its transcript. The expression modulation of all three actin-bindingproteins was observed to occur specifically in the entorhinally denervated zones:the stratum lacunosum-moleculare of the hippocampus and the outer molecularlayer of the dentate gyrus, where energetic glial phagocytosis of degeneratedaxonal and terminal debris had taken place. The double staining of in situhybridization with either IB4 (microglial marker) histochemistry or GFAP(astroglial marker) immunohistorchemistry showed that in the denervated zonesactivated microglial cells were responsible for the transcript increase of profilinand Tβ4, while gelsolin was highly expressed by both activated microglia andastrocytes following the deafferentation. The results suggest that thespatiotemporal upregulation of three actin-binding proteins profilin, gelsolin andTβ4 in the deafferented hippocampus is induced by transections of the entorhinalafferents and that these proteins may be involved in glial activation which isassociated with morphological change, migration, and phagocytic behavior of glialcells.