Abstract:
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.
摘要:
社会隔离和孤独导致认知能力下降是老年人的严重健康问题。尽管CapsosiphonFulvescens(Cf-hGP)的亲水性糖蛋白可预防衰老引起的认知障碍,其对社会隔离导致的认知功能障碍的影响尚不清楚.这项研究调查了Cf-hGP对老年大鼠认知功能障碍的功效,并描述了其潜在机制。口服Cf-hGP(15mg/kg/d,4周)逆转了社会隔离诱导的细胞外信号调节蛋白激酶1/2(ERK1/2)磷酸化下降,突触后密度蛋白95和α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体亚基1,并增加了海马背侧突触体中代谢型谷氨酸受体5的表达。此外,Cf-hGP预防了社会隔离引起的空间记忆障碍,其作用通过抑制ERK1/2或Cf-hGP的去糖基化而减弱。Cf-hGP诱导的ERK1/2介导的突触后密度蛋白95在背侧海马中的聚集改善了社会孤立的老年大鼠的记忆形成,和蛋白质糖基化有助于增强Cf-hGP效应。