Involvement of non-neuronal cells in entorhinal-hippocampal reorganization following lesions.

Abstract

Entorhinal lesion leads to anterograde degeneration of perforant path fibers in their main hippocampal termination zones. Subsequently, remaining fibers sprout and form new synapses on the denervated dendrites. This degeneration and reorganization is accompanied by sequential changes in glial morphology and function. Within a few hours following the lesion, amoeboid microglia migrate into the zone of denervation. Some hours later, signs of activation can be seen on astrocytes in the zone of denervation, where both cell types proliferate and remain in an activated state for more than two weeks. These activated glial cells might be involved in lesion-induced plasticity in at least two ways: (1) by releasing cytokines and growth factors which regulate layer-specific sprouting and (2) by phagocytosis of axonal debris, because myelin sheaths act as obstacles for sprouting fibers in the central nervous system. Whereas direct evidence for the former is still missing, the latter was investigated using phagocytosis-dependent labeling techniques. Both microglial cells and astrocytes incorporate axonal debris. Phagocytosing microglial cells develop the immune phenotype of antigen-presenting cells, whereas astrocytes strongly express FasL (CD95L), which induces apoptosis of activated lymphocytes. Thus, the interaction of glial cells with immune cells might be another, previously underestimated, aspect of reorganization following entorhinal lesion.