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微管蛋白集体太赫兹振荡的麻醉改变与临床效能相关:对麻醉作用和术后认知功能障碍的影响。

Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency: Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction.

机构信息

Departments of Psychology & Neuroscience, Computer Science, and Clinical Immunology, and the Clinical Systems Biology Group, Institute for Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA.

National Human Genome Center and Department of Medicine, Howard University College of Medicine, and Computational Physics Laboratory, Howard University, Washington, DC, USA.

出版信息

Sci Rep. 2017 Aug 29;7(1):9877. doi: 10.1038/s41598-017-09992-7.


DOI:10.1038/s41598-017-09992-7
PMID:28852014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5575257/
Abstract

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.

摘要

麻醉会阻断意识和记忆,而不影响非意识的大脑活动。虽然麻醉作用的确切机制尚不清楚,但 Meyer-Overton 相关性将麻醉效力与类似脂质的非极性介质中的溶解度联系起来。麻醉作用还与麻醉剂的疏水性、永久偶极和极化率有关,并被认为发生在大脑蛋白质中的类似脂质的非极性区域内。通常,麻醉剂的蛋白质靶标被假定为神经元膜受体和离子通道,然而新的证据表明,它对神经元内微管有重要影响,由于其在术后认知功能障碍 (POCD) 中的潜在作用,微管成为一个关注的靶点。在这里,我们使用微管蛋白(微管的蛋白质亚基)的结合位点预测,结合分子对接模拟、量子化学计算和微管中集体偶极相互作用的理论建模,研究了包括麻醉剂、非麻醉剂和麻醉/惊厥剂在内的一组气体对微管蛋白动力学的影响。我们发现,这些气体以与其麻醉效力相关的方式改变了集体太赫兹偶极子的振荡。了解麻醉作用可能有助于揭示意识的大脑机制,并在选择和开发用于治疗神经退行性疾病患者的手术麻醉剂时,最大程度地减少对微管骨架有影响的术后认知功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/77421268f966/41598_2017_9992_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/bbe0634dadb7/41598_2017_9992_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/76094895def8/41598_2017_9992_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/030f803ed67b/41598_2017_9992_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/77421268f966/41598_2017_9992_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/bbe0634dadb7/41598_2017_9992_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/76094895def8/41598_2017_9992_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/030f803ed67b/41598_2017_9992_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb70/5575257/77421268f966/41598_2017_9992_Fig4_HTML.jpg

相似文献

[1]
Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency: Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction.

Sci Rep. 2017-8-29

[2]
Anesthetics act in quantum channels in brain microtubules to prevent consciousness.

Curr Top Med Chem. 2015

[3]
Computational predictions of volatile anesthetic interactions with the microtubule cytoskeleton: implications for side effects of general anesthesia.

PLoS One. 2012-6-25

[4]
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J Biomol Struct Dyn. 2022-10

[5]
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[6]
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Acc Chem Res. 2010-1-19

[7]
Large-scale molecular dynamics simulations of general anesthetic effects on the ion channel in the fully hydrated membrane: the implication of molecular mechanisms of general anesthesia.

Proc Natl Acad Sci U S A. 2002-12-10

[8]
The role of electrostatic interactions in governing anesthetic action on the torpedo nicotinic acetylcholine receptor.

Anesth Analg. 2002-8

[9]
[Centennial for the Meyer-Overton rule: anesthetics and receptors].

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[10]
Binding site and affinity prediction of general anesthetics to protein targets using docking.

Anesth Analg. 2012-3-5

引用本文的文献

[1]
Old theory, new evidence: inhalational anesthetics disrupt a collective quantum state of intraneuronal microtubules to cause unconsciousness.

Med Gas Res. 2026-6-1

[2]
The concept of biophotonic signaling in the human body and brain: rationale, problems and directions.

Front Syst Neurosci. 2025-6-23

[3]
A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems.

Neurosci Conscious. 2025-5-6

[4]
The impact of ketamine and thiopental anesthesia on ultraweak photon emission and oxidative-nitrosative stress in rat brains.

Front Syst Neurosci. 2025-3-21

[5]
Microtubule-modulating drugs alter sensitivity to isoflurane in mice.

BMC Anesthesiol. 2025-2-28

[6]
Microtubule-Stabilizer Epothilone B Delays Anesthetic-Induced Unconsciousness in Rats.

eNeuro. 2024-8

[7]
Emergence of information processing in biological systems and the origin of life.

Commun Integr Biol. 2024-7-10

[8]
Anesthesia and the neurobiology of consciousness.

Neuron. 2024-5-15

[9]
Ultra weak photon emission-a brief review.

Front Physiol. 2024-2-14

[10]
An In Silico Investigation of the Molecular Interactions between Volatile Anesthetics and Actin.

Pharmaceuticals (Basel). 2023-12-26

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