Editors' ChoiceElectroconvulsive Shock Therapy

Joule Thief?

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Science Translational Medicine  29 Feb 2012:
Vol. 4, Issue 123, pp. 123ec36
DOI: 10.1126/scitranslmed.3003900

Many are shocked to learn that electroconvulsive therapy is an effective—and likely underutilized—treatment for medically refractory depression. The therapeutic effects of electroconvulsive shock (ECS) are thought to be mediated by neuroplastic changes, but the mechanisms are still unknown. Now, Yanpallewar and colleagues show that the scaffold protein tamalin is critical for ECS-induced neuroplasticity.

Proteins such as tamalin provide an organizing “scaffold” for a complex of interrelated cellular signaling molecules that includes metabotropic glutamate receptors. Yanpallewar et al. used a mouse model to demonstrate that ECS leads to an up-regulation of tamalin mRNA and protein in the hippocampus, a brain region involved in memory and a site of adult neurogenesis. Deletion of the tamalin gene did not have any obvious depressive behavioral effects in mice, but these mice did show a reduction in ECS-induced neurogenesis in the hippocampus. Furthermore, the neuronal sprouting that is normally associated with ECS was attenuated after deletion of tamalin. Last, loss of tamalin also blocked ECS-induced long-term potentiation, which is a form of neural plasticity.

This translational study provides compelling molecular, cellular, and neurophysiologic evidence that the scaffold protein tamalin is critical for the neural changes triggered by ECS. Whether tamalin participates in the effects of human electroconvulsive therapy is not known but is an important question to answer. If it does, pharmacological modulation of tamalin could improve the efficacy of ECT or potentially bypass ECT—and its accompanying side effects—altogether. Providing a nonelectrical pathway to achieve the same positive effects as ECT would mark tamalin as the ultimate joule thief.

S. U. Yanpallewar et al., Tamalin is a critical mediator of electroconvulsive shock-induced adult neuroplasticity. J. Neurosci. 32, 2252–2262 (2012). [Abstract]

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