The persisting effects of electroconvulsive stimulation on the hippocampal proteome

• ECS induces protein changes in the hippocampus.
• Four weeks after chronic ECS there are persisting protein changes in the hippocampus.
• Cytoskeletal- and metabolism-related proteins were identified following ECS.
• Chronic+4 weeks ECS induced change in the cytoskeletal protein actin confirmed by immunoblot.

Electroconvulsive therapy (ECT) is the most acutely effective treatment available for severe depression. However, its mechanism of action is not fully understood. Elucidating the protein changes induced in the brain by ECT will enhance our understanding of this antidepressant therapy. Electroconvulsive stimulation (ECS), the animal analogue of ECT, was administered to rats to determine the proteomic changes induced in the hippocampus, a region of the brain implicated in the biology of depression and its treatment. Two-dimensional difference in gel electrophoresis (2D-DiGE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were applied to identify differentially expressed proteins following acute (×1 treatment), chronic (×10 treatments) or chronic+4 weeks (×10 treatments plus 4 weeks later) ECS. Administration of acute, chronic and chronic+4 weeks ECS induced significant changes in multiple DiGE gel protein spots. Interestingly, the largest number of differentially expressed protein spots was identified following chronic+4 weeks ECS. Following protein identification by LC-MS/MS, gene ontology analysis primarily implicated proteins with cytoskeletal and metabolism-related roles in the action of ECS. Immunoblotting confirmed the changes in abundance of the cytoskeletal protein actin following chronic+4 weeks ECS. Overall, chronic+4 weeks ECS was particularly effective at inducing longer-lasting changes in the abundance of hippocampal proteins with cytoskeletal and metabolism roles. These results suggest a role for persisting cytoskeletal-related neuroplastic changes in the action of ECS and may be informative as to the antidepressant mechanisms of ECT in patients with depression.