Journal of Molecular Neuroscience

, Volume 70, Issue 1, pp 112–119 | Cite as

High Concentration of Ketone Body β-Hydroxybutyrate Modifies Synaptic Vesicle Cycle and Depolarizes Plasma Membrane of Rat Brain Synaptosomes

  • Polina P. Voronina
  • Ksenia V. Adamovich
  • Tatyana V. Adamovich
  • Tatsiana G. Dubouskaya
  • Sviatlana V. Hrynevich
  • Tatsiana V. Waseem
  • Sergei V. FedorovichEmail author


Ketoacidosis is a dangerous complication of diabetes mellitus in which plasma levels of ketone bodies can reach 20–25 mM. This condition is life-threatening. In contrast, a ketogenic diet, achieving plasma levels of ketone bodies of about 4–5 mM, can be used for treating different brain diseases. However, the factors leading to the conversion of the neuroprotective ketone bodies’ action to the neurotoxic action during ketoacidosis are still unknown. We investigated the influence of high concentration (25 mM) of the main ketone body, β-hydroxybutyrate (BHB), on intrasynaptosomal pH (pHi), synaptic vesicle cycle, plasma membrane, and mitochondrial potentials. Using the fluorescent dye BCECF-AM, it was shown that BHB at concentrations of 8 and 25 mM did not influence pHi in synaptosomes. By means of the fluorescent dye acridine orange, it was demonstrated that 25 mM of BHB had no effect on exocytosis but inhibited compensatory endocytosis by 5-fold. Increasing buffer capacity with 25 mM HEPES did not affect endocytosis. Glucose abolished BHB-induced endocytosis inhibition. Using the fluorescent dye DiSC3(5), it was shown that 25 mM of BHB induced a significant plasma membrane depolarization. This effect was not impacted by glucose. Using the fluorescent dye rhodamine-123, it was shown that BHB alone (25 mМ) did not alter the potential of intrasynaptosomal mitochondria.

Importantly, the high concentration of BHB (25 mМ) causes the depolarization of the plasma membrane and stronger inhibition of endocytosis compared with the intermediate concentration (8 mM).


Synaptosomes Ketone bodies Ketoacidosis Diabetes mellitus Plasma membrane potential Endocytosis 



We thank Mr. John Evans for English language editing to improve the manuscript.

Author Contribution

PV: synaptosomal experiments, analysis and interpretation of data, and editing of manuscript. KA: synaptosomal experiments, analysis and interpretation of data, and editing of manuscript. TA: synaptosomal experiments, analysis and interpretation of data, and editing of manuscript. TD: synaptosomal experiments, analysis and interpretation of data, and editing of manuscript. SH: synaptosomal experiments and editing of manuscript. TW: contribution to conception and editing of manuscript. SF: substantial contribution to conception, synaptosomal experiments, analysis and interpretation of data, writing of manuscript and project management.

Funding Information

This work was supported by the Bielorussian Republican Foundation of Basic Investigation (grants B17-006 and B19-001).

Compliance with Ethical Standards

Conflict of Interests

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Polina P. Voronina
    • 1
  • Ksenia V. Adamovich
    • 1
  • Tatyana V. Adamovich
    • 1
  • Tatsiana G. Dubouskaya
    • 1
  • Sviatlana V. Hrynevich
    • 1
  • Tatsiana V. Waseem
    • 2
  • Sergei V. Fedorovich
    • 1
    • 3
    Email author
  1. 1.Laboratory of Immunology and Cell BiophysicsInstitute of Biophysics and Cell EngineeringMinskBelarus
  2. 2.Department of PharmacologyUniversity of OxfordOxfordUK
  3. 3.Department of BiochemistryBelarusian State UniversityMinskBelarus

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