Transgenic mice expressing the human presenilin 1 gene demonstrate enhanced hippocampal reorganization following entorhinal cortex lesions.

We have examined the effects of the presence of the mutated human presenilin 1 gene (M146L; hps1*) on lesion-induced sprouting in the hippocampus of the mouse (C57/CBA). The entorhinal cortex was unilaterally lesioned with ibotenic acid in adult, male mice. Four weeks later the subsequent axonal sprouting in the dentate gyrus was analysed, by measuring the density of the synaptophysin immunocytochemical staining in the termination area of the entorhinal cortex axons. The data demonstrate that mice expressing either the human presenilin 1 gene (hps1) or the hps1* gene display a significantly increased density of immunocytochemical staining for synaptophysin, indicative of axonal sprouting, compared to the control mice. No (or a very small) sprouting response is observed in mice expressing the normal mouse ps1 gene. Taken together, these data indicate that the presence of a human ps1 gene, normal or with an Alzheimer's disease mutation, leads to enhanced plasticity in the mouse brain.