Institute of Anatomy, Department of Cell and Neurobiology, Humboldt-University Hospital Charité, Berlin, Germany
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.
