Lesion of the rat entorhinal cortex leads to a rapid microglial reaction in the dentate gyrus

Abstract

Stereotaxic lesioning of the entorhinal cortex leads to an anterograde axonal degeneration in the molecular layer of the dentate gyrus. As revealed by immunocytochemical and histochemical methods, lesion of the entorhinal cortex induced a proliferation of microglia and an increased expression of established microglial activation markers within the deafferented zone. Reactive microglial cells were detected as early as 24 h after the lesion. The microglial reaction showed a maximum around day 3 post-lesion and disappeared by day 8 post-lesion. Reactive microglia were strongly positive for the B4-isolectin from Griffonia simplicifolia (GSI-B4), expressed high levels of CR3 complement receptor and 5'-nucleotidase, but lacked CD4 and MHC class I and II antigens. In addition, microglial cells were identified using MUC 102, a new monoclonal antibody against rat microglia. At the ultrastructural level, reactive microglial cells were consistently seen to phagocytose degenerating terminals. Our data suggest that (1) axonal degeneration represents a sufficient stimulus for inducing microglial activation and proliferation in the deafferented dentate gyrus; (2) these activated microglial cells are characterized by immunophenotypes different from those observed in other types of CNS injury; (3) the early microglial reaction precedes the well-documented astrocyte reaction in the dentate gyrus; and (4) the timed interaction of microglia and astrocytes could be important for regulating regenerative sprouting processes in the mature CNS.

Region-specific activation of microglial cells in the rat septal complex following fimbria-fornix transection

“…The strong microglial reaction including phagocytotic activity associated with anterograde fiber and terminal degeneration observed in the LS resembles the changes reported for other models of deafferentation. For example, deafferentation of dentate granule cells by entorhinal lesion leads to a massive activation of astrocytes and microglial cells (e.g., Fagan and Gage, 1990;Gehrmann et al, 1991;Lee et al, 1997). However, the moderate and short-lasting initial response of microglial cells in the MS containing the axotomized septohippocampal projection neurons contrasted to the heavy microglial reaction in other lesion paradigms.…”

Reduction in 50-kHz call-numbers and suppression of tickling-associated positive affective behaviour after lesioning of the lateral hypothalamic parvafox nucleus in rats

“…Iba1 is a calcium-binding protein specifically expressed in microglia [65], which are activated in regions where cell death and inflammation occur (see, for example, [66]). Microglia were considered to be activated if they were present at high density and if they manifested an enlarged soma with relatively few cytoplasmic processes.…”

CXCR3-Dependent Microglial Recruitment Is Essential for Dendrite Loss after Brain Lesion

“…The fibers from the entorhinal cortex form the cortical input to the hippocampus. Axotomy of this tract causes a rapid astroglial and microglial reaction in the deafferentiated middle and outer molecular layers of the dentate gyrus, whereas the inner molecular layer is not affected (Gall et al, 1979;Gehrmann et al, 1991;Jensen et al, 1994Jensen et al, , 1999Bechmann and Nitsch, 1997;Hailer et al, 1999). This reaction involves morphological and functional changes, such as phagocytic activity and a loss of ramification (Bechmann and Nitsch, 1997).…”