Repeated Electroconvulsive Shock Transiently Affects Cognition and Neurometabolism in Mice

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective intervention for drug-resistant depression. Despite clinical relevance, ECT is underutilized due to hypothetical adverse effects on cognitive functions. This study aims to investigate the short-term and long-term effects of repeated electroconvulsive shock (ECS) on cognition and cerebral glucose metabolism in a mouse model. METHODS: Two-month-old C57BL/6NCrl male mice were subjected to 7 sessions of ECS under isoflurane anesthesia in a sham-controlled manner. The spatial working memory was assessed using the Y-maze test after 24 hours and 3 months of the last ECS session. The neurometabolic activity was evaluated via intravenous administration of [1,6-13C2]glucose in awake mice, followed by measurement of 13C labeling of brain metabolites by ex vivo 1H-[13C]-NMR spectroscopy. RESULTS: Repeated ECS led to impaired spatial working memory (ECS: 59.4 ± 6.0%, sham: 68.9 ± 6.7%; P = 0.042; t = 2.3, df = 10) together with perturbed neurometabolite homeostasis such as increased taurine (9.6 ± 0.1 vs 8.9 ± 0.2 μmol/g; Padj < 0.001; t = 7.1, df = 10), and glycerophosphocholine (1.17 ± 0.05 vs 1.06 ± 0.02 μmol/g; Padj = 0.010), and decreased choline (0.12 ± 0.00 vs 0.13 ± 0.01 μmol/g; Padj = 0.019) and phosphocholine (0.50 ± 0.02 vs 0.55 ± 0.02 μmol/g; Padj = 0.011) levels in the cerebral cortex after 24 hours. ECS mice exhibited a transient reduction in the rate of glucose oxidation in glutamatergic neurons (0.352 ± 0.023 vs 0.397 ± 0.024 μmol/g/min; Padj = 0.027; t = 2.6, df = 10) in the cerebral cortex. Interestingly, ECS-induced acute cognitive and neurometabolic deficiencies disappeared after 3 months. CONCLUSIONS: Repeated ECS led to transient impairment in cognition and neurometabolism, and cognitive deficits correlated with reduced cerebral glucose metabolism. These findings might be helpful to clinicians in addressing concerns about electroconvulsive therapy.