Hinard, V. et al., Key Electrophysiological, Molecular, and Metabolic Signatures of Sleep and Wakefulness Revealed in Primary Cortical Cultures. Journal of Neuroscience, 2012. 32(36): 12506-12517.


Metabolon results led to:
Validation of an in vitro model for studying sleep/wake cycles
New insight into the role sleep plays in reestablishing neuronal membrane homeostasis

Key metabolomic observations:
Glycolysis was upregulated during wakefulness or cell stimulation
Lysolipids were dramatically elevated during wakefulness or cell stimulation

Sleep is thought to potentiate restorative processes and sleep deprivation to hinder them. Understanding these processes could potentially lead to interventions to support recovery from prolong periods of wakefulness. Thus, investigators sought to develop and qualify an in vitro model that recapitulates the circadian rhythmicity observed in sleep. To do this, they compared cortical cultures to brain tissue from a mouse model using physiological assays, gene expression profiling and metabolomics. The culture system exhibited remarkably similar metabolic pathway changes compared to the animals (increased glycolysis and fatty acid oxidation). In addition, an unexpected observation was an impact on membrane phospholipids which, when combining this pattern with gene expression data, suggests that sleep reestablished neuronal membrane homeostasis. By demonstrating that sleep patterns can be recapitulated with this in vitro model, the way is paved to investigate the molecular underpinnings and pharmacology of sleep–wake states.

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