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

Abstract：

: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.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

Jang S,Kim H,Jeong J,Lee SK,Kim EW,Park M,Kim CH,Lee JE,Namkoong K,Kim E

doi

10.1016/j.pnpbp.2016.06.011

subject

Has Abstract

pub_date

2016-11-03 00:00:00

pages

57-65

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(16)30100-2

journal_volume

pub_type

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