Microglial reactivity correlates to the density and the myelination of theanterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata

Transection of the entorhino-dentate perforant path is a well known model f or lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecul ar layer of the SJL/J and C57BI/6 mouse. The morphological transformation o f the microglial cells and their densitometrically measured Mac-1 immunorea ctivity were correlated with the density of silver-impregnated axonal and t erminal degeneration and the myelination of the degenerating medial and lat eral perforant pathways. Anterograde axonal and terminal degeneration leads to: (i) altered myelin basic protein immunoreactivity with the appearance of discrete myelin deposits preferentially in the denervated medial and sig nificantly less so in the lateral perforant path zone from day 2 after lesi oning; (ii) an increase in number and Mac-1 immunoreactivity of morphologic ally-changed microglial cells in the denervated perforant path zones with m ore pronounced morphological transformation of microglia in the medial than in the lateral perforant path zones at day 2 but not day 5 after lesioning ; and (iii) a linear correlation between the density of microglial Mac-1 re activity and axonal degeneration in the medial but not in the lateral perfo rant path zone at two days postlesion, and a linear correlation in both zon es at five days postlesion. We propose that the differentiated microglial response is due to the differ ent densities of axonal and terminal degeneration, as observed in the indiv idual cases. The finding of a potentiated or accelerated microglial activat ion in the medial as compared to the lateral perforant path zone suggests d ifferent kinetics of microglial activation in areas with degenerating myeli nated and unmyelinated fibers. (C) 1999 IBRO. Published by Elsevier Science Ltd.