Sequential upregulation of cell adhesion molecules in degenerating rat basal forebrain cholinergic neurons and in phagocytotic microglial cells |
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Authors: | Hartlage-Rübsamen M Schliebs R |
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Affiliation: | Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Jahnallee 59, D-04109, Leipzig, Germany. |
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Abstract: | To study the functional role of adhesion molecules in neurodegenerative events in vivo, the basal forebrain cholinergic lesion-induced expression of the intercellular adhesion molecule (ICAM)-1 and leukocyte function-associated antigen (LFA)-1 was studied by double immunocytochemistry and Western blot analysis. A single intracerebroventricular application of the cholinergic immunotoxin, 192IgG-saporin, produced a selective cholinergic cell loss in rat basal forebrain nuclei detectable by gradual loss of choline acetyltransferase (ChAT)-immunoreactive cells starting 3 days but being nearly complete 7 days after injection of the toxin. The degeneration of cholinergic neurons was accompanied by a striking appearance of activated microglial cells in the lesioned areas. Four days following injection of 192IgG-saporin, ICAM-1 immunoreactivity was predominantly observed in ChAT-positive neurons and partly in activated microglia in the basal forebrain nuclei, while LFA-1 expression at this time point was restricted to neurons. However, 7 days after cholinergic lesion, only a few, shrunken neuronal somata were found to be immunoreactive for ICAM-1 and LFA-1, while activated microglial cells demonstrated strong immunoreactivity for ICAM-1 and LFA-1 in the lesioned forebrain areas, persisting up to 14 days after lesion while no immunoreactivity was observed in neurons at this time point. Western blot analysis demonstrated increased ICAM-1 level in the basal forebrain already detectable 4 days after surgery but being more pronounced 7 days post lesion. The data suggest that ICAM-1 and LFA-1 may act as intercellular recognition signals by which degenerating cholinergic neurons actively participate in the sequence of events leading to their targeting and elimination by phagocytotic microglia. |
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Keywords: | Cholinergic immunotoxin 192IgG-saporin Neuronal degeneration Microglia ICAM-1 LFA-1 |
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