Li isotopes differentiation in neuronal activity – evidence for novel quantum effects in neuroscience

ORAL

Abstract





It has recently been proposed that quantum effects, including nuclear spin effects, may be operational in the brain. In our work, we studied the role of the two stable isotopes of lithium (Li) to elicit a Li isotope differentiation in neuronal activity. While natural Lithium salts have been a frontline medication for the treatment of bipolar disorder (BD), the role of Li isotopes remains largely unexplored. In the past, two studies reported puzzling different effects of Li isotopes on animal behavior of rats. In addition, recent theoretical works have proposed that the two lithium isotopes could induce distinct neurological effects due to quantum effects arising from their distinct nuclear spin but direct experimental evidence has been lacking.

Using multielectrode array (MEA) electrophysiology, we discovered that the two lithium isotopes have a very large and opposite effect on the electrical activity of rat hippocampus slices, affecting differently both synaptic transmission and synaptic plasticity. These results directly indicate that the two Li isotopes have different ways in affecting electrical neuronal activity in the brain, circumventing the less direct and possibly ambiguous evidence from the two aforementioned previous animal behavior studies. In addition, we tested several biochemical targets, such as GSK-3β kinase, actively scrutinized as a potential target for Li action; explored the effects of Li isotopes on cell viability in HT-22 neuronal cells and in mitochondria Ca exchange via the sodium-calcium-lithium exchanger (NCLX). No isotope differentiation was observed within these specific biochemical targets. The search for the molecular mechanisms continues, with the goal to uncover the quantum phenomena that can explain the large isotope differentiation effect observed in electrical activity of neuronal tissues.

* New Frontiers in Research Fund, IONIS Phramaceutical, Transformative Quantum Technologies Seed Grant, CFREF University of Waterloo

Publication: 1. K. Esmaielpour, M.J.P. Gingras, Z. Leonenko, J. Mielke. Giant and Opposite Lithium Isotope Effects on Electrical Activity in Rat Brain Hippocampus Slices. To be submitted.

2. M.L. Deline, J. Straub, M. Patel, P. Subba, M. Grashei, F.H.A. van Heijster, P. Pirkwieser, J.D. Livingstone, M. Beazely, B. Kendall, MJP. Gingras, Z. Leonenko, C. Höschen, G. Harrington, K. Küllmer, F. Schilling, M. Fisher, M. Helgeson, T. Fromme, Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity. Frontiers in Physiology, 2023; 14: 1200119.

3. J.D. Livingstone, M.J.P. Gingras, Z. Leonenko, M.A. Beazely. Search for Lithium Isotope Effects in Neuronal HT22 cells. Biophysics and Biochemistry Reports, 2023, 34: 101461.

4. I. Bukhteeva, FA. Rahman, R. Duncan, J. Quadrilatero, B. Kendall, E. Pavlov, MJP. Gingras, Z. Leonenko, Lithium isotopes effect on Ca efflux through sodium/lithium/calcium exchanger (NCLX) in heart mitochondria. To be submitted.

Presenters

  • Zoya Leonenko

    University of Waterloo

Authors

  • Khadijeh Esmaeilpour

    University of Waterloo

  • Irina Bukhteeva

    University of Waterloo

  • James D Livingstone

    University of Waterloo

  • Michael Beazely

    University of Waterloo

  • Evgeny Pavlov

    New York University

  • Brian Kendall

    University of Waterloo

  • John Mielke

    University of Waterloo

  • Michel J Gingras

    University of Waterloo

  • Zoya Leonenko

    University of Waterloo