Effects of Li isotopes in neurodegeneration: molecular and quantum neuroscience

Speaker: 
Dr. Zoya Leonenko
Institution: 
Department of Physics and Astronomy
Department of Biology
Waterloo Institute for Nanotechnology
University of Waterloo, Canada
Date: 
Thursday, May 2, 2024
Time: 
11:00 am
Location: 
ISEB 6610

About the speaker: Dr. Zoya Leonenko has PhD in Chemical Physics, has expertise in nanoscale biophysics and scanning probe microscopy, is the author of over 90 scientific publications, and is a former President of Biophysical Society of Canada. Current research interests include biophysics of lipids and lipid-protein interactions, the role of structural changes and physical properties of lipid membrane in controlling biological processes and diseases, application of lipid films in biomedical nanotechnology; atomic force microscopy; surface plasmon resonance; nanopore electrophysiology.  Specific focus is on understanding molecular mechanisms of neurodegeneration including Alzheimer’s disease and bipolar disorder. Recently together with collaborators she initiated a new research program in quantum biology, which has a focus to uncover new quantum phenomena in biology and neuroscience.

 

Abstract:  The remarkable neurological effects of lithium (Li) salts as a mood stabilizer were discovered by Cade in 1949 and since then Li has been a leading medication in the treatment of bipolar disorder for over sixty years and the potential benefits of Li in mitigating against other neurological disorders such as Alzheimer’s disease are attracting growing interest. It has recently been proposed that quantum effects, including nuclear spin effects, may be operational in the brain, but experimental evidence is lacking. 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.

We studied the role of the two stable isotopes of lithium (Li) to elicit a Li isotope differentiation in neuronal activity, mitochondrial function and neuroprotection. 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, 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), as well mechanism of membrane neuroprotection in Alzheimer’s disease. No isotope differentiation was observed within these specific biochemical or biophysical 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.

Host: 
Albert Siryaporn