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Blunted response of hippocampal AMPK associated with reduced neurogenesis in older versus younger mice

 Sooah Jang  ;  Hyunjeong Kim  ;  Jihyeon Jeong  ;  Su Kyoung Lee  ;  Eun Woo Kim  ;  Minsun Park  ;  Chul Hoon Kim  ;  Jong Eun Lee  ;  Kee Namkoong  ;  Eosu Kim 
 Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol.71 : 57-65, 2016 
Journal Title
 Progress in Neuro-Psychopharmacology & Biological Psychiatry 
Issue Date
AMP-Activated Protein Kinases/metabolism* ; Adenosine Triphosphate/metabolism ; Aging/drug effects ; Aging/pathology* ; Aminoimidazole Carboxamide/analogs & derivatives ; Aminoimidazole Carboxamide/pharmacology ; Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Bromodeoxyuridine/metabolism ; Gene Expression Regulation/drug effects ; Hippocampus/drug effects ; Hippocampus/enzymology* ; Hippocampus/physiopathology* ; Hypoglycemic Agents/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/metabolism ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Neurogenesis/drug effects ; Neurogenesis/physiology* ; Neuropeptides/metabolism ; Ribonucleotides/pharmacology
AMPK ; Aging ; BDNF ; Hippocampus ; Neurogenesis
The rate of hippocampal neurogenesis declines with aging. This is partly explained by decreased neural responsiveness to various cues stimulating metabolism. AMP-activated protein kinase (AMPK), a pivotal enzyme regulating energy homeostasis in response to metabolic demands, showed the diminished sensitivity in peripheral tissues during aging. AMPK is also known to be involved in neurogenesis. We aimed to see whether AMPK reactivity is also blunted in the aged hippocampus, and thus is associated with aging-related change in neurogenesis. Following subchronic (7days) intraperitoneal and acute intracerebroventricular (i.c.v.) administration of either 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR; AMPK activator) or saline (sham) to young (16-week-old) and old (72-week-old) mice, we measured changes in AMPK activity, brain-derived neurotrophic factor (BDNF) expression or neurogenesis in the hippocampus. AICAR-induced changes in AMPK activity were observed in the hippocampus of young mice after acute i.c.v. injection. However, neither subchronic nor acute treatment induced significant changes in AMPK activity in old mice. Intriguingly, directions of AICAR-induced changes in AMPK activity were opposite between the hippocampus (decrease) and skeletal muscle (increase). ATP levels were inversely correlated with hippocampal AMPK activity, suggesting that the higher energy levels achieved by AICAR treatment might deactivate neuronal AMPK in young mice. The blunted response of AMPK to AICAR in old age was also indicated by the observations that the levels of neurogenesis and BDNF expression were significantly changed only in young mice upon AICAR treatment. Our findings suggest that the blunted response of neuronal AMPK in old age might be responsible for aging-associated decline in neurogenesis. Therefore, in addition to activation of AMPK, recovering its sensitivity may be necessary to enhance hippocampal neurogenesis in old age.
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1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Behavioral Sciences in Medicine (의학행동과학연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Namkoong, Kee(남궁기) ORCID logo https://orcid.org/0000-0003-1400-8057
Park, Min Sun(박민선)
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Jang, Soo Ah(장수아)
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