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Frontiers in Neuroenergetics ·

Volume 3 - 2011 | https://doi.org/10.3389/fnene.2011.00007

Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens

  • Tünde Molnár1
  • László Héja1
  • Zsuzsa Emri2
  • Ágnes Simon1
  • Gabriella Nyitrai1
  • Ildikó Pál1
  • Julianna Kardos1*corresponding author
  1. 11 Department of Neurochemistry, Chemical Research Center, Hungarian Academy of Sciences Budapest, Hungary
  2. 22 Department of Zoology, Eszterházy Károly College Eger, Hungary
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Abstract

Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca 2+ transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca 2+ transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca 2+ transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca 2+ dynamics evoked by GHB suggested that Ca 2+ was released from internal stores. Similarly to SUC, the GHB response was also characterized by an effective concentration of 50 μM. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca 2+ signal remained in mice lacking GABA B receptor type 1 subunit in the presence and absence of the N -Methyl- d -Aspartate (NMDA) receptor antagonist (2 R )-amino-5-phosphonovaleric acid (APV), indicating action mechanisms independent of the GABA B or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252, and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91) also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca 2+ signaling in astrocytic networks.

Keywords

References

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Citation

Molnár, T., et al. (2011). Activation of Astroglial Calcium Signaling by Endogenous Metabolites Succinate and Gamma-Hydroxybutyrate in the Nucleus Accumbens. Frontiers in Neuroenergetics, Volume 3. https://doi.org/
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3 - 2011

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Copyright © 2011 Molnár, Héja, Emri, Simon, Nyitrai, Pál and Kardos.

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*Correspondence: Julianna Kardos

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