Restoring the pattern of perineuronal net sulphation corrects age-related memory loss

Memory loss is a usual consequence of ageing. In aged brains, perineuronal nets (PNNs), which limit neuroplasticity and are implicated in memory, become inhibitory due to decreased 6-sulphation of their glycan chains (C6S). Aged mice show progressive deficits in memory tasks, but removal of PNNs or digestion of their glycans rescued age-related memory loss. Reduction of permissive C6S by transgenic deletion of 6-sulfotransferase led to very early memory loss. However, restoring C6S levels in aged animals by AAV delivery or transgenic expression of 6-sulfotransferase restored memory. Low C6S levels caused loss of cortical long-term potentiation, which was restored by AAV-mediated 6-sulfotransferase delivery. The study shows that loss of C6S in the aged brain leads to declining memory and cognition, which can be restored by C6S replacement.