title: Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.
abstract: Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups, whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment.
authors.affiliation: Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.
authors.forename: Suna
authors.initials: S
authors.lastname: Kang
authors.affiliation: Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.
authors.forename: Na Rang
authors.initials: NR
authors.lastname: Moon
authors.affiliation: Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea.
authors.forename: Da Sol
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Division of Endocrinology & Metabolism, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Republic of Korea. Electronic address: smpark@hoseo.edu.
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D054439:Ghrelin; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Cognitive function; Energy; Ghrelin; Glucose; Tau