Hydrophilic Glycoproteins of an Edible Green Alga Capsosiphon fulvescens Prevent Aging-Induced Spatial Memory Impairment by Suppressing GSK-3β-Mediated ER Stress in Dorsal Hippocampus

• Published in: Marine drugs 2019-03, Vol.17 (3), p.168
• Main Authors: Oh, Jeong Hwan, Nam, Taek-Jeong
• Format: Article
• Language: English
• Subjects: Age; Ageing; Aging; Aging (artificial); Animal behavior; Antibodies; Aquatic plants; Attenuation; Brain-derived neurotrophic factor; c-Jun protein; Capsosiphon fulvescens; Cognitive ability; cognitive dysfunction; Endoplasmic reticulum; endoplasmic reticulum stress; Extracellular; Extracellular signal-regulated kinase; Gastric cancer; Glycogen; Glycogen synthase kinase 3; Glycogens; Glycoproteins; Growth factors; Hippocampus; Hydrophilicity; Impairment; JNK protein; Kinases; Matrix metalloproteinases; Memory; Memory tasks; Metalloproteinase; Neurodegenerative diseases; Neurogenesis; Oral administration; Phosphorylation; Physiology; Proteins; Receptors; Spatial analysis; Spatial memory; Transcription factors; Tyrosine
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17030168

Endoplasmic reticulum (ER) stress is involved in various neurodegenerative disorders. We previously found that ( ) crude proteins enhance spatial memory by increasing the expression of brain-derived neurotrophic factor (BDNF) in rat dorsal hippocampus. The present study investigated whether the chronic oral administration of hydrophilic glycoproteins (Cf-hGP) reduces aging-induced cognitive dysfunction by regulating ER stress in the dorsal hippocampus. The oral administration of Cf-hGP (15 mg/kg/day) for four weeks attenuated the aging-induced increase in ER stress response protein glucose-regulated protein 78 (GRP78) in the synaptosome of the dorsal hippocampus; this was attenuated by the function-blocking anti-BDNF antibody (1 μg/μL) and a matrix metallopeptidase 9 inhibitor 1 (5 μM). Aging-induced GRP78 expression was associated with glycogen synthase kinase-3 beta (GSK-3β) (Tyr216)-mediated c-Jun N-terminal kinase phosphorylation, which was downregulated upon Cf-hGP administration. The Cf-hGP-induced increase in GSK-3β (Ser9) phosphorylation was downregulated by inhibiting tyrosine receptor kinase B and extracellular signal-regulated kinase (ERK)1/2 with cyclotraxin-B (200 nM) and SL327 (10 μM), respectively. Cf-hGP administration or the inhibition of ER stress with salubrinal (1 mg/kg, i.p.) significantly decreased aging-induced spatial memory impairment. These findings suggest that the activation of the synaptosomal BDNF-ERK1/2 signaling in the dorsal hippocampus by Cf-hGP attenuates age-dependent ER stress-induced cognitive dysfunction.