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

Document Type

Article

Publication Date

2-1-2019

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 [ 1 H-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.

Identifier

85056774854 (Scopus)

Publication Title

Behavioural Brain Research

External Full Text Location

https://doi.org/10.1016/j.bbr.2018.10.021

e-ISSN

18727549

ISSN

01664328

PubMed ID

30342064

First Page

312

Last Page

319

Volume

359

Grant

SFB 779

Fund Ref

Deutscher Akademischer Austauschdienst

This document is currently not available here.

Share

COinS