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
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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
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Zoya Leonenko
University of Waterloo
Authors
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Khadijeh Esmaeilpour
University of Waterloo
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Irina Bukhteeva
University of Waterloo
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James D Livingstone
University of Waterloo
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Michael Beazely
University of Waterloo
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Evgeny Pavlov
New York University
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Brian Kendall
University of Waterloo
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John Mielke
University of Waterloo
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Michel J Gingras
University of Waterloo
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Zoya Leonenko
University of Waterloo