Neurochemical Research

, Volume 40, Issue 12, pp 2493–2504 | Cite as

Monoaminergic Control of Cellular Glucose Utilization by Glycogenolysis in Neocortex and Hippocampus

  • Mauro DiNuzzoEmail author
  • Federico Giove
  • Bruno Maraviglia
  • Silvia Mangia
Original Paper


Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90 % inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system modulates both function and metabolism of forebrain regions in a manner mediated by glycogen mobilization in astrocytes.


Astrocytes Glycogen Glucose Monoamines 



5-Hydroxytryptamine (serotonin)


Adenylate kinase


Creatine kinase




Glucose 6-phosphate


Glucose transporter


Glycogen phosphorylase






Locus coeruleus




Norepinephrine (noradrenaline)


Na+/K+-activated adenosine triphosphatase


Raphe nucleus


Tricarboxylic acid


Tuberomammillary nucleus


Ventral tegmental area



The author S. M. thanks the Grant NIH 1R01DK099137 from the National Institute of Health (NIH) for support.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Magnetic Resonance for Brain Investigation LaboratoryMuseo Storico della Fisica e Centro di Studi e Ricerche “Enrico Fermi”RomeItaly
  2. 2.Dipartimento di FisicaSapienza Università di RomaRomeItaly
  3. 3.Fondazione Santa Lucia IRCCSRomeItaly
  4. 4.Department of Radiology, Center for Magnetic Resonance ResearchUniversity of MinnesotaMinneapolisUSA
  5. 5.Magnetic Resonance for Brain Investigation LaboratoryRomeItaly

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