Memory Improving Effects in Social-Isolated Aged Rats by Seaweed Glycoproteins

Abstract

Social isolation and loneliness that could induce cognitive decline are serious public health problems in elderly. The trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is a critical process in long-term potentiation of synapses that is necessary for memory formation. We previously found that glycoproteins of an edible seaweed Capsosiphon fulvescens (C. fulvescens) prevent aging-induced cognitive impairment via regulation of brain-derived neurotrophic factor in hippocampus. This study was to investigate whether chronic administration of hydrophilic glycoproteins of C. fulvescens (Cf-hGP) prevent cognitive dysfunctions caused by social isolation in aged rats and this effect is regulated by post synaptic density protein 95 (PSD-95)-mediated AMPAR trafficking and the glycosylation of Cf-hGP. Social isolation for four weeks decreased phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2), PSD-95 (Ser295) and AMPAR GluR1 (Ser845) and increased expression of metabotropic glutamate receptor 5 (mGluR5) in synaptosome of the dorsal hippocampus, which was attenuated by chronic Cf-hGP treatment (15 mg/kg/day, 4 weeks). Blockade of mGluR5 abolished decrease in ERK1/2-mediated phosphorylation of PSD-95 (Ser295) and GluR1 (Ser845) in the socially isolated rats. In particular, chronic Cf-hGP treatment enhanced binding of ERK1/2 to PSD-95 and upregulated the surface movement of AMPAR GluR1 in the dorsal hippocampus. In addition, Cf-hGP treatment prevented spatial memory impairment caused by the social isolation, which was attenuated by inhibition of ERK1/2 or deglycosylation of Cf-hGP. These findings suggest that Cf-hGP-induced clustering of ERK1/2-mediated PSD-95 in the dorsal hippocampus improves memory formation in socially isolated aged rats and protein glycosylation contributes to enhancing the Cf-hGP effect.