Impacts of Electroconvulsive Therapy on the Neurometabolic Activity in a Mice Model of Depression: An Ex Vivo 1H-[13C]-NMR Spectroscopy Study

Abstract

Electroconvulsive therapy (ECT) is an effective treatment for severe and drug-resistant depression, yet its mode of action remains poorly understood. This study aimed to evaluate the effects of ECT on neurometabolism using ex vivo 1H-[13C]-NMR spectroscopy in conjunction with intravenous infusion of [1,6-13C2]glucose in a chronic variable mild stress (CVMS) model of depression. Both CVMS and control mice were subjected to seven sessions of electroconvulsive shock under mild isoflurane anesthesia. The CVMS mice exhibited a reduction in sucrose preference (CVMS 67.1 ± 14.9%, n = 5; CON 86.5 ± 0.6%, n = 5; p = 0.007), and an increase in immobility duration (175.9 ± 22.6 vs. 92.0 ± 23.0 s, p < 0.001) in the forced-swim test. The cerebral metabolic rates of glucose oxidation in glutamatergic (CMRGlc(Glu)) (CVMS 0.134 ± 0.015 µmol/g/min, n = 5; CON 0.201 ± 0.045 µmol/g/min, n = 5; padj = 0.04) and GABAergic neurons (CMRGlc(GABA)) (0.030 ± 0.002 vs. 0.046 ± 0.011 µmol/g/min, padj = 0.04) were reduced in the prefrontal cortex (PFC) of CVMS mice. ECT treatment in CVMS mice normalized sucrose preference [F(1,27) = 0.0024, p = 0.961] and immobility duration [F(1,28) = 0.434, p = 0.515], but not the time spent in the center zone (CVMS + ECT 10.4 ± 5.5 s, CON + sham 22.3 ± 11.4 s, padj = 0.0006) in the open field test. The ECT-treated CVMS mice exhibited reduced (padj = 0.021) CMRGlc(Glu) in PFC (0.169 ± 0.026 µmol/g/min, n = 8) when compared with CVMS mice, which underwent the sham procedure (0.226 ± 0.030 µmol/g/min, n = 8). These observations are consistent with ECT’s anticonvulsant hypothesis for its anti-depressive action.