TY - JOUR
T1 - Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency
T2 - Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction
AU - Craddock, Travis J.A.
AU - Kurian, Philip
AU - Preto, Jordane
AU - Sahu, Kamlesh
AU - Hameroff, Stuart R.
AU - Klobukowski, Mariusz
AU - Tuszynski, Jack A.
N1 - Funding Information:
TJAC would like to acknowledge financial support from the Department of Psychology and Neuroscience, the Institute for Neuro-Immune Medicine at Nova Southeastern University (NSU), and the NSU President’s Faculty Research and Development Grant (PFRDG) program PFRDG 335426 (Craddock – PI). PK would also like to acknowledge partial financial support from the Whole Genome Science Foundation. This research was also partly supported by a grant from NSERC (Canada) awarded to JAT. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the funding agencies.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic's hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
AB - Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic's hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
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U2 - 10.1038/s41598-017-09992-7
DO - 10.1038/s41598-017-09992-7
M3 - Article
C2 - 28852014
AN - SCOPUS:85028456785
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 9877
ER -