Social isolation and loneliness inducing cognitive decline are serious health problems in the elderly. Although the hydrophilic glycoproteins of Capsosiphon fulvescens (Cf-hGP) prevent aging-induced cognitive impairment, its effects on social isolation-induced cognitive dysfunction are unclear. This study investigated the efficacy of Cf-hGP against cognitive dysfunction in aged rats and delineated its underlying mechanisms. The oral administration of Cf-hGP (15 mg/kg/d, 4 weeks) reversed the social isolation-induced decreases in phosphorylation of extracellular signal‑regulated protein kinase 1/2 (ERK1/2), postsynaptic density protein 95, and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit 1 and increased expression of metabotropic glutamate receptor 5 in the synaptosome of the dorsal hippocampus. Furthermore, Cf-hGP prevented social isolation-induced spatial memory impairment, and its effects were attenuated by inhibition of ERK1/2 or deglycosylation of Cf-hGP. Cf-hGP-induced clustering of ERK1/2-mediated postsynaptic density protein 95 in the dorsal hippocampus improves memory formation in socially isolated aged rats, and protein glycosylation contributes to enhancing the Cf-hGP effect.
Keywords: Extracellular signal‑regulated protein kinase 1/2; Metabotropic glutamate receptor 5; Postsynaptic density protein 95; Synaptic clustering; α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor.
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