Nutritional status, cognition, and survival: a new role for leptin and AMP kinase.
Although adequate nutrition is essential for optimal neural activity and survival, mild energy restriction may improve cognition and prolong longevity. Energy status is monitored by the cellular AMP-activated protein kinase (AMPK) system, whereas leptin regulates total energy balance. We investigated the roles of AMPK and leptin in cognition and survival under diet restriction (DR). Hippocampal AMPK activity increases with energy restriction. Modest activation (DR to 60%) induces neurogenesis and improves cognition. However, DR to 40% augmented AMPK activity, reduced cognition and catecholamines, and increased neural apoptosis and mortality. Leptin signaling is preserved only in DR to 60%, countering the effects of AMPK "overactivation" by preventing neuroapoptosis, restoring noradrenergic activity and behavioral performance, and increasing longevity. The balance between leptin and AMPK is crucial in determining neuronal fate, cognitive ability, and survival. Should these findings extend to Man, then controlled activation of AMPK may improve neurodegenerative diseases, and leptin may have a new role in treating stress-associated malnutrition.
Dagon
Yossi
Y
Department of Human Nutrition and Metabolism, Braun School of Public Health, Faculty of Medicine, Hebrew University-Hadassah Medical School, Jerusalem 91120.
Avraham
Yosefa
Y
Magen
Iddo
I
Gertler
Arie
A
Ben-Hur
Tamir
T
Berry
Elliot M
EM
D000263:Adenylate Kinase / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002395:Catecholamines / Q000378:metabolism; D003071:Cognition; D017931:DNA Primers; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D007150:Immunohistochemistry; D020738:Leptin / Q000502:physiology*; D008136:Longevity; D009752:Nutritional Status; D016716:PC12 Cells; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D002395:Catecholamines; D017931:DNA Primers; D020738:Leptin; D000263:Adenylate Kinase