Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2010, Article ID 153657, 13 pages
Review Article

Effects of S100B on Serotonergic Plasticity and Neuroinflammation in the Hippocampus in Down Syndrome and Alzheimer's Disease: Studies in an S100B Overexpressing Mouse Model

1Departments of Surgery, Neurosurgery, and Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, College of Medicine, Scott & White Hospital, Central Texas Veterans Health System, Temple, TX 76504, USA
2Program in Biopsychology, Department of Psychology, State University of New York, Stony Brook, NY 11794-2500, USA
3Department of Psychology, Dowling College, Oakdale, NY 11769, USA

Received 10 March 2010; Revised 1 June 2010; Accepted 2 July 2010

Academic Editor: Rosario Donato

Copyright © 2010 Lee A. Shapiro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


S100B promotes development and maturation in the mammalian brain. However, prolonged or extensive exposure can lead to neurodegeneration. Two important functions of S100B in this regard, are its role in the development and plasticity of the serotonergic neurotransmitter system, and its role in the cascade of glial changes associated with neuroinflammation. Both of these processes are therefore accelerated towards degeneration in disease processes wherein S100B is increased, notably, Alzheimer's disease (AD) and Down syndrome (DS). In order to study the role of S100B in this context, we have examined S100B overexpressing transgenic mice. Similar to AD and DS, the transgenic animals show a profound change in serotonin innervation. By 28 weeks of age, there is a significant loss of terminals in the hippocampus. Similarly, the transgenic animals show neuroinflammatory changes analogous with AD and DS. These include decreased numbers of mature, stable astroglial cells, increased numbers of activated microglial cells and increased microglial expression of the cell surface receptor RAGE. Eventually, the S100B transgenic animals show neurodegeneration and the appearance of hyperphosphorylated tau structures, as seen in late stage DS and AD. The role of S100B in these conditions is discussed.