Role of the cell adhesion molecule F3/contactin in synaptic plasticity and memory in aged mice.

F3/contactin (F3), a cell-adhesion molecule belonging to the immunoglobulin supergene family, is involved in several aspects of neural development including synapse building, maintenance and functioning. By using a transgenic (Tg) model where F3 overexpression was induced under control of regulatory sequences from the human TAG-1 (TAX-1) gene (TAG/F3 mice), we have previously demonstrated that F3 plays a role in adult hippocampal neurogenesis, synaptic plasticity and memory. Based on these findings, and because F3 levels physiologically decrease with age, here we aimed to investigate whether its overexpression might counteract the age-related cognitive decline. We used 20-24 month-old wild type as a model of physiological aging, age-matched TAG/F3 mice and 3 month-old wild type mice (control). Old TAG/F3 homozygous mice presented an improvement of CA1 long-term potentiation, spatial learning, reference and recognition memory compared with old wild type. Tg aged mice also presented an increase of the pro-apoptotic molecules Caspase-3 and Bax, and a concomitant increase of the anti-apoptotic and plasticity-related pathway BDNF/CREB/Bcl-2. Interestingly, amyloid-precursor protein (APP) processing was shifted toward sAPPα with a consequent decrease of sAPPβ and Aβ levels. In conclusion, our data suggest that F3/contactin plays a role in hippocampal synaptic plasticity and memory in aged mice, probably by acting on molecular pathways related to apoptosis and Aβ production.