Spatial and nonspatial learning in mice: effects of S100 beta overexpression and age.

S100 beta, a Ca2+ binding astrocytic brain protein implicated in brain development and neurophysiology, has elevated levels in progressive neurodegenerative diseases, Down's Syndrome, and Alzheimer Disease. Transgenic mice carrying multiple S100 beta gene copies exhibited abnormal exploratory behaviors and synaptic processes suggesting hippocampal dysfunction. Here we analyze learning in a hippocampal-dependent (spatial) as well as a non-hippocampal-dependent (nonspatial) version of the Morris water maze and compare CD1 control and CD1-derived S100 beta transgenic mice. We also investigate possible progressive age-dependent effects of S100 beta overexpression by comparing two age groups of the above mice: 3- and 16-month-old. We show that 3-month-old S100 beta transgenic mice have a spatial task-specific impairment confirming a hippocampal dysfunction. However, we found the 16-month-old transgenic mice statistically indistinguishable from their normal counterparts, a result that does not confirm progressive S100 beta transgene effects. We also show that age, independently of the transgene, impairs spatial learning, spares nonspatial learning and reference memory, but leads to behavioral rigidity.