Activation of BDNF-mediated PKA signaling in the ventral hippocampus by Capsosiphon fulvescens glycoproteins alleviates depressive-like behavior in aged rats

[Display omitted] •Cf-hGP downregulated immobility time of aged rats in forced swimming test.•mBDNF expression in the ventral hippocampus was upregulated by Cf-hGP.•BDNF-mediated PKA signaling by Cf-hGP increased AMPAR GluR1 phosphorylation.•Activation of PKA signaling by Cf-hGP also decreased JNK-mediated ER stress.•AMPAR blockade or PKA inhibition abolished Cf-hGP-induced decrease in immobility time. 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.