INDUCTION OF MICROGLIAL IMMUNOMOLECULES BY ANTEROGRADELY DEGENERATINGMOSSY FIBERS IN THE RAT HIPPOCAMPAL-FORMATION

Degeneration of myelinated axonal connections is generally held to pro vide a strong stimulus for microglial expression of major histocompati bility complex (MHC) class II antigen. The present study demonstrates that strong microglial reactions also are induced by axonal and termin al degeneration of the unmyelinated hippocampal mossy fibres. After de struction of dentate granule cells by focal injections of colchicine ( or transection of the mossy fibres) in adult rats, immunocytochemical analysis of the mossy fibre terminal fields in the dentate hilus and r egio inferior of hippocampus proper (CA3) revealed profound changes in microglial cells with increased expression of the complement receptor type 3 and induction of MHC class I antigen, leukocyte common antigen , lymphocyte function-associated antigen-1 and MHC class II antigen. T he microglial reaction, first detectable 4 days after the lesion, beca me maximal during the third postlesional week, and had almost vanished 6 weeks after the lesion. From recent studies we know that anterograd e degeneration of myelinated Schaffer-collaterals from CA3 to regio su perior of hippocampus proper and myelinated entorhinal perforant path fibres to fascia dentata is accompanied by microglial expression of MH C class I antigen, but not class II. Together with the present finding s, this demonstrates that myelin debris is neither necessary nor suffi cient to induce expression of microglial MHC class II antigen within t he hippocampus.