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AMPK activation regulates neuronal structure in developing hippocampal neurons.

S Ramamurthy1, E Chang1, Y Cao1

  • 1Department of Neuroscience, Johns Hopkins University School of Medicine, 855 N Wolfe Street, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, 855 N Wolfe Street, Baltimore, MD 21205, USA.

Neuroscience
|December 4, 2013
PubMed
Summary

AMP-activated protein kinase (AMPK) regulates neuronal development. Activating this energy sensor inhibits neuron growth and structure formation during development by impacting mTOR and Akt pathways.

Keywords:
4′,6-diamidino-2-phenylindole5-aminoimidazole-4-carboxamide-1-b-d-ribofuranoside5′-adenosine monophosphate-activated protein kinaseADPAICARAMPAMPKATPBRSKBSACaMKKβDAPIDIVDPBSDulbecco’s phosphate-buffered salineGSK-3βHBSSHNHank’s balanced salt solutionKOLKB1MTORMap2P13KPVDFRT-PCRSDSTBSTTris-buffered saline+Tween 20WTadenosine diphosphateadenosine monophosphateadenosine triphosphateaxonbovine serum albuminbrain-specific kinasecalcium/calmodulin-dependent kinase kinase βdays in vitrodendritedevelopmentglycogen synthase kinase 3βhippocampal neuronsknockoutliver kinase B1mammalian target of rapamycinmetabolismmicrotubule-associated protein 2neuronp70 ribosomal protein S6 kinasep70S6kphosphatidyl inositol 3-kinasepolyvinylidene difluoridereverse transcriptase-polymerase chain reactionsodium dodecyl sulfatewild type

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • AMP-activated protein kinase (AMPK) is a key energy sensor regulating cellular metabolism.
  • The AMPK complex comprises catalytic α, regulatory β, and AMP/ATP-binding γ subunits, with various isoforms.
  • The role of specific AMPK complexes in neuronal structure development remains largely uncharacterized.

Purpose of the Study:

  • To investigate the expression and function of AMPK subunits in developing hippocampal neurons.
  • To determine how AMPK activation affects neuronal development at different stages.
  • To elucidate the signaling pathways through which AMPK influences neuronal structure.

Main Methods:

  • Examined AMPK subunit expression during hippocampal neuron development.
  • Activated AMPK using energetic stress to observe effects on neuronal structure.
  • Analyzed the impact of AMPK activation on mTOR and Akt signaling pathways.

Main Results:

  • AMPK subunit expression increases during neuronal development.
  • Activation of AMPK by energetic stress inhibits axon outgrowth, dendrite growth, and arborization.
  • A single functional AMPK complex is sufficient to mediate these inhibitory effects.
  • AMPK activation suppresses both mTOR and Akt signaling pathways.

Conclusions:

  • The energy-sensing AMPK pathway plays a critical role in regulating neuronal structure during development.
  • AMPK influences neuronal development at multiple stages and in distinct neuronal regions.
  • AMPK's effects on neuronal structure are mediated through the suppression of mTOR and Akt signaling.