AMPK signaling regulates the age-related decline of hippocampal neurogenesis

Brian Z. Wang, Jane J. Yang, Hongxia Zhang, Charity A. Smith, Kunlin Jin

Research output: Contribution to journalArticle

Abstract

The global incidence of age-associated neurological diseases is expected to rise with increasingly greying societies. In the aged brain, there is a dramatic decrease in the number of stem cells, which is a main cause for the decrease in brain function. Intrinsic factors, such as cell metabolism, have been studied but its role in neurogenesis is still unknown. Therefore, this study sought to establish whether AMP-activated protein kinase (AMPK) signaling does indeed regulate hippocampal neurogenesis in the aged brain. We found that i) AMPKα2 was the predominant catalytic subunit in the subgranular and subventricular zones; ii) AMPK activation was at a significantly higher level in the aged vs. young hippocampus; iii) short term (7 days) treatment with selective AMPK signaling inhibitor Compound C (10 mg/kg/day, i.p.) significantly increased the numbers of newborn (BrdU+), Type 2 (MCM2+), and Type 3 (DCX+) neural stem cells, but not Type 1 (GFAP+/Sox2+) cells, in the aged hippocampus. Taken together, our results demonstrate that AMPK signaling plays a critical role in the age-related decline of hippocampal neurogenesis.

Original languageEnglish
Pages (from-to)1058-1074
Number of pages17
JournalAging and Disease
Volume10
Issue number5
DOIs
StatePublished - 1 Jan 2019

Fingerprint

AMP-Activated Protein Kinases
Neurogenesis
Hippocampus
Brain
Intrinsic Factor
Neural Stem Cells
Lateral Ventricles
Bromodeoxyuridine
Protein Kinase Inhibitors
Catalytic Domain
Stem Cells
Incidence

Keywords

  • Aging
  • AICAR
  • AMPK
  • Compound C
  • Metabolism
  • Stem cell

Cite this

Wang, Brian Z. ; Yang, Jane J. ; Zhang, Hongxia ; Smith, Charity A. ; Jin, Kunlin. / AMPK signaling regulates the age-related decline of hippocampal neurogenesis. In: Aging and Disease. 2019 ; Vol. 10, No. 5. pp. 1058-1074.
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AMPK signaling regulates the age-related decline of hippocampal neurogenesis. / Wang, Brian Z.; Yang, Jane J.; Zhang, Hongxia; Smith, Charity A.; Jin, Kunlin.

In: Aging and Disease, Vol. 10, No. 5, 01.01.2019, p. 1058-1074.

Research output: Contribution to journalArticle

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