title: Biosynthesis of glycerol phosphate is associated with long-term potentiation in hippocampal neurons.
abstract: BACKGROUND
  Neurons have a very high energy requirement, and their metabolism is tightly regulated to ensure delivery of adequate substrate to sustain neuronal activity and neuroplastic changes. The mechanisms underlying the regulation of neuronal metabolism, however, are not completely clear.
  
  
  OBJECTIVE
  The objective of this study was to investigate the central carbon metabolism in neurons, in order to identify the regulatory pathways governing neuronal anabolism and catabolism.
  
  
  METHODS
  Here we first have applied MS-based endometabolomics to elucidate the metabolic dynamics in cultured hippocampal primary neurons. Using nanoLC-ESI-LTQ Orbitrap MS approach followed by statistical analysis, we measure the dynamics of uniformly labeled13C-glucose entering neurons. We adapted the method by coupling offline patch-clamp setup with MS to confirm findings in vivo.
  
  
  RESULTS
  According to non-parametric statistical analysis of metabolic dynamics, in cultured hippocampal neurons, the glycerol phosphate shuttle is active and correlates with the metabolic flux in the pentose phosphate pathway. In the hippocampus, glycerol-3-phosphate biosynthesis was activated in response to long-term potentiation together with the upregulation of glycolysis and the TCA cycle, but was inactive or silenced in basal conditions.
  
  
  CONCLUSIONS
  We identified the biosynthesis of glycerol-3-phosphate as a key regulator in mechanisms implicated in learning and memory. Notably, defects in enzymes linked with the glycerol phosphate shuttle have been implicated in neurological disorders and intellectual disability.These results could improve our understanding of the general mechanisms of learning and memory and facilitate the development of novel therapies for metabolic disorders linked with intellectual disability.
authors: Institute of Neuroscience, CNR, Via L. Vanvitelli 32, 20129 Milan, Italy.
authors: Giuseppe
authors: 0000-0002-5963-4580
authors: G
authors: Martano
authors: Institute of Neuroscience, CNR, Via L. Vanvitelli 32, 20129 Milan, Italy.
authors: Luca
authors: L
authors: Murru
authors: Institute of Neuroscience, CNR, Via L. Vanvitelli 32, 20129 Milan, Italy.
authors: Edoardo
authors: E
authors: Moretto
authors: Institute of Neuroscience, CNR, Via L. Vanvitelli 32, 20129 Milan, Italy.
authors: Laura
authors: L
authors: Gerosa
authors: Fondazione IRCCS, Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy.
authors: Giulia
authors: G
authors: Garrone
authors: Fondazione IRCCS, Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milan, Italy.
authors: Vittorio
authors: V
authors: Krogh
authors: Institute of Neuroscience, CNR, Via L. Vanvitelli 32, 20129 Milan, Italy.
authors: Maria
authors: M
authors: Passafaro
keywords: Glucose metabolism; Glycerol phosphate; Hippocampus; Long term potentiation; Mass spectrometry; Primary neurons