“…The hypofunction of NMDAR is primarily responsible for deficits in synaptic plasticity in aged animals or patients with age-related neurodegenerative diseases (Barnes et al, 1997;Shankar et al, 1998;Potier et al, 2000;Clayton et al, 2002;Mothet et al, 2006;Battaglia et al, 2007). Moreover, recent studies demonstrate that the alteration in NMDAR functional properties, rather than in their expression or density, is the mechanism of age-related deficits in NMDAR (Potier et al, 2000;Clayton et al, 2002;Boric et al, 2008;Turpin et al, 2009). Interestingly, D-serine, an amino acid that serves as an endogenous ligand for the strychnine-insensitive glycine-binding site of NMDAR, rescues the impaired NMDARdependent synaptic plasticity in aged animals (Mothet et al, 2006), suggesting that the upregulation of NMDAR activity by pharmacological approach can reverse age-associated impairment of synaptic function.…”