Polysialylated neural cell adhesion molecule modulates photic signaling in the mouse suprachiasmatic nucleus

Polysialic acid (PSA), a sialic acid polymer that regulates plasticity and cell-cell interactions in neural tissues, is expressed in the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). In vivo enzymatic removal of PSA from the mouse SCN significantly impaired both the photic induction of Fos protein in SCN cells and light-induced phase-resetting of the circadian locomotor activity rhythm. Genetic deletion of PSA and it's neural cell adhesion molecule (NCAM) carrier correspondingly attenuated light-induced circadian phase-shifting. Comparison of PSA levels between young and old mice revealed a large aging-related reduction in SCN PSA content that accompanies the diminished capacity for circadian photic response reported in old rodents. Collectively these data support the contention that PSA modulates photic signaling in the SCN, and that normal reductions in the cell surface molecule contribute to aging-related deficits in SCN circadian clock function.