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  Neuronal glutamatergic changes and peripheral markers of cytoskeleton dynamics change synchronically 24 h after sub-anaesthetic dose of ketamine in healthy subjects

Colic, L., McDonnell, C., Li, M., Woelfer, M., Liebe, T., Kretzschmar, M., et al. (2019). Neuronal glutamatergic changes and peripheral markers of cytoskeleton dynamics change synchronically 24 h after sub-anaesthetic dose of ketamine in healthy subjects. Behavioural Brain Research, 359, 312-319. doi:10.1016/j.bbr.2018.10.021.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-97BC-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-97BD-F
Genre: Journal Article

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 Creators:
Colic, L, Author
McDonnell, C, Author
Li, M, Author
Woelfer, M, Author
Liebe, T, Author
Kretzschmar, M, Author
Speck, O, Author
Schott, BH, Author
Bianchi, M, Author
Walter, M1, 2, Author              
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Ketamine acts as a rapid–acting antidepressant by restoring glutamatergic deficits and activating synaptic plasticity processes, with peak activity 24 h after infusion. Microtubule dynamics are known to play a key role in modulation of cytoskeleton and synaptic plasticity, as well as in signalling events in peripheral blood cells. Here, we correlated ketamine-induced change in glutamate/creatinine (Glu/Cr) levels in the pregenual anterior cingulate cortex (pgACC) with peripheral markers of microtubule dynamics, namely acetylated α-tubulin (Acet-Tub), with particular attention to gender specificity. Eighty healthy controls (age = 25.89 ± 5.29, 33 women) were administered intravenous infusion of either ketamine (0.5 mg/kg) or placebo (saline). Blood samples were obtained at baseline and 24 h after infusion and plasma levels of Acet-Tub and transferrin (TRF; loading control) were measured via infrared western blotting. Glu/Cr levels were measured via high-field (7 T) proton magnetic resonance spectroscopy [1H-MRS] in the pgACC at the same time points. Gender differences were observed in baseline Acet–Tub/TRF levels (p < 0.001), and an interaction of time by treatment by gender (F = 5.13, p = 0.027) was found, with a significant increase in Acet–Tub/TRF for ketamine group in females only (p = 0.038). Ketamine-induced gender-independent Glu/Cr changes at 24 h (F(1, 69) = 4.08, p = 0.047), and changes in the pgACC were negatively correlated with the Acet-Tub/TRF expression (r= -0.464, p = 0.010) in the ketamine group, in which, separated by sex, only women showed significant correlation. Our findings indicate a temporal association between changes in central ketamine-induced glutamatergic effects and peripheral markers of cytoskeleton reorganization, particularly in females.

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 Dates: 2018-102019-02
 Publication Status: Published in print
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 Table of Contents: -
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 Identifiers: DOI: 10.1016/j.bbr.2018.10.021
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Title: Behavioural Brain Research
Source Genre: Journal
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Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 359 Sequence Number: - Start / End Page: 312 - 319 Identifier: ISSN: 0166-4328
CoNE: https://pure.mpg.de/cone/journals/resource/954925482632