Spatial and Nonspatial Learning in Mice: Effects of S100β Overexpression and Age

1986). It is due to the duplication of a critical region of chromosome 21 involving a potentially large number of genes (Epstein, 1987). The roles these genes may play in human neurodegenerative diseases are mainly unknown. To dissect the effects of these genes one may apply single gene manipulation molecular techniques. Transgenic technology, for instance, allows one to express a candidate gene in vivo in mammalian organisms such as mice. Phenotypical analysis of such genetically altered mice may help us understand the functional properties of the gene of interest and the role it plays in vivo. A candidate gene from the 21 chromosome has been the gene encoding S100β, a 20-kDa Ca2+ binding brain protein whose levels are elevated in Down’s Syndrome (DS) and Alzheimer Disease (AD) (Griffin, Stanley, Ling, White, MacLeod, Perrot, White, & Araoz, 1989). Based on in vitro observations, S100β protein has been suggested to be a paracrine neurotrophic factor in the brain promoting glial cell proliferation (Selinfreund, Barger, Pledger, & Van Eldik, 1991) and neurite outgrowth (Kligman & Hsieh, 1987; Azmitia, Dolan, & Whitaker-Azmitia, 1990; Van Eldik, Christie-Pope, Bolin, Shooter, & Whestell, 1991). S100β has also been shown to affect long-term potentiation (Lewis & Teyler, 1986; Fazeli, Errington, Dolphin, & Bliss, 1990), a neurophysiological phenomenon associated with learning processes (Bliss & Collingridge, 1993). Experiments with transgenic mice demonstrated that overexpression of S100β significantly alters a range of potentially hippocampal-dependent behavioral processes including open field exploratory behavior (Gerlai, Friend, Becker, O’Hanlon, Marks, & Roder, 1993; Gerlai & Roder, 1993), T-maze spontaneous alternation (Gerlai, Marks, & Roder, 1994a) and exploration (Roder, Roder, & Gerlai, 1996a), and learning (Gerlai,