Neuronal glutamatergic changes and peripheral markers of cytoskeleton dynamics change synchronically 24 h after sub-anaesthetic dose of ketamine in healthy subjects.
Lejla Colic, Conor McDonnell, Meng Li, Marie Woelfer, Thomas Liebe, Moritz Kretzschmar, Oliver Speck, Björn H Schott, Massimiliano Bianchi, Martin Walter
Behavioural Brain Research February 1, 2019 DOI: 10.1016/j.bbr.2018.10.021 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Healthy controls (age 25.89 ± 5.29 years, 33 women) |
| Interventions | Ketamine Saline |
| Dose | 0.5 mg/kg |
| Duration | 24-hour follow-up after infusion |
| Measures | Acet-Tub/TRF via infrared western blotting, Glu/Cr via proton magnetic resonance spectroscopy (1H-MRS) |
| Topics | Ketamine Esketamine |
| Keywords | Acet-tub Blood markers Gender specificity Glutamatergic system |
| Key findings | Ketamine increased pgACC Glu/Cr at 24 hours in both sexes, while Acet-Tub/TRF rose only in women. Ketamine-induced Glu/Cr change correlated negatively with Acet-Tub/TRF in the ketamine group (r = -0.464), a correlation significant only among women, suggesting a sex-specific temporal link between central glutamatergic effects and peripheral cytoskeleton markers. |
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.