Aging is associated with an increased risk of emotional disorders such as depression. In this study, effects of Capsosiphon fulvescens hydrophilic glycoproteins (Cf-hGP) on depressive-like behavior in aged rats were investigated. Oral administration of Cf-hGP (15 mg/kg/day; 4 weeks) attenuated immobility time of aged rats in forced swimming test by increasing expression of mature brain-derived neurotrophic factor (BDNF) in the ventral hippocampus. Cf-hGP-induced BDNF-mediated activation of extracellular signal-regulated kinase (ERK)1/2 increased cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) phosphorylation, which upregulated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 phosphorylation at serine 845. The activation of BDNF-mediated PKA signaling by Cf-hGP also attenuated endoplasmic reticulum (ER) stress in the ventral hippocampus. AMPAR blockade or PKA inhibition abolished the Cf-hGP-induced decrease in immobility time. These findings suggest that BDNF-mediated cAMP/PKA signaling in the ventral hippocampus contributes to antidepressant effects of Cf-hGP by regulating AMPAR GluA1 phosphorylation and ER stress.

衰老与情绪障碍如抑郁症的风险增加有关。在这项研究中，Capsosiphon fulvescens的作用研究了亲水性糖蛋白（Cf-hGP）对衰老大鼠的抑郁样行为。口服Cf-hGP（15 mg / kg /天； 4周）可通过增加腹侧海马中成熟的脑源性神经营养因子（BDNF）的表达来减少强迫游泳试验中老年大鼠的不动时间。Cf-hGP诱导的BDNF介导的细胞外信号调节激酶（ERK）1/2的激活增加了环磷酸一腺苷（cAMP）的水平和蛋白激酶A（PKA）的磷酸化，从而上调了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的丝氨酸845磷酸化。Cf-hGP对BDNF介导的PKA信号的激活也减弱了腹侧海马的内质网（ER）应激。AMPAR阻滞或PKA抑制作用消除了Cf-hGP诱导的固定时间减少。