Reduced anxiety in the mice expressing mutant (N141I) presenilin 2

Alzheimer's disease (AD) is characterized by progressive cognitive impairment. The effect of presenilin 1 (PS1) and PS2 mutation on cognition has been well characterized in a variety of transgenic mice. However, noncognitive behaviors have not been considered in these mice. In the present study, we found that transgenic mice expressing mutant PS2 (N141I) displayed decreased anxiety behavior determined by the elevated plus maze test and the light dark box test. However, these mice showed biphasic ambulatory activity (hyperactivity followed by hypoactivity) in an open field test. Correlated well with the reduced anxiety, expression of GABA(A)alpha(1) receptor was higher whereas c-Fos was lower in the cortex, hippocampus, and amygdala of the mice expressing PS2 mutation than those of the wild-type PS2 or nontransgenic control mice. These data indicate that PS2 mutation causes reduction of anxiety, and this effect may be related to the change of the expression of GABA(A)alpha(1) receptor and c-Fos. These findings could be useful in the understanding and the treatment of AD patients.