Expression levels of cytoskeletal proteins indicate pathological aging of S100B transgenic mice: an immunohistochemical study of MAP-2, drebrin and GAP-43

S100B is a calcium-binding protein found within astroglial cells. When released, S100B has extracellular neurotrophic effects involving the neuronal cytoskeleton. The gene for S100B is located on chromosome 21 and levels of the protein are elevated in Down Syndrome (DS) and Alzheimer's Disease (AD). Thus, overexpression of S100B may be related to the cytoskeletal abnormalities seen in these disorders. Transgenic mice overexpressing human S100B were examined for cytoskeletal changes as young (70 days) and aged (200 days) adults, using immunochemical staining of the dendritic associated protein, MAP-2, the growth-associated protem-43 (GAP-43) and the dendritic spine marker, drebrin. As young adults, the S100B transgenic mice exhibited significantly greater MAP-2-immunoreactivity in the hippocampus, however as older adults, the animals exhibited less staining. In both the CD1 control animals and the S100B animals, the immunoreactivity of drebrin increased with age, however there were no significant between group differences. Finally, the older S100B animals showed more GAP-43 staining than the control animals, suggesting that synaptic remodeling could take place, possibly in response to the loss of MAP-2-ir dendrites. Overall, the data suggest that S100B overexpression leads to changes in cytoskeletal markers. The longitudinal effects of S100B overexpression are discussed with relevance to aging and pathology. (C) 2004 Elsevier B.V. All rights reserved.