Electroconvulsive seizures (ECS) do not prevent LPS-induced behavioral alterations and microglial activation.

E M Van Buel,U L M Eisel,H C Klein,F J Bosker,J Van Drunen,J Strijker,W Douwenga

doi:10.1186/s12974-015-0454-x

Abstract

BackgroundLong-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain.MethodsAdult male C57Bl/6J mice received a series of ten electroconvulsive seizures (ECS) or sham shocks, followed by an intracerebroventricular (i.c.v.) lipopolysaccharide (LPS) or phosphate-buffered saline (PBS) injection. Brains were extracted and immunohistochemically stained for the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1). In addition, a sucrose preference test and an open-field test were performed to quantify behavioral alterations.ResultsLPS induced a short-term reduction in sucrose preference, which normalized within 3 days. In addition, LPS reduced the distance walked in the open field and induced alterations in grooming and rearing behavior. ECS did not affect any of these parameters. Phenotypical analysis of microglia demonstrated an LPS-induced increase in microglial activity ranging from 84 to 213 % in different hippocampal regions (CA3 213 %; CA1 84 %; dentate gyrus 131 %; and hilus 123 %). ECS-induced alterations in microglial activity were insignificant, ranging from −2.6 to 14.3 % in PBS-injected mice and from −20.2 to 6.6 % in LPS-injected mice.ConclusionsWe were unable to demonstrate an effect of ECS on LPS-induced microglial activity or behavioral alterations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0454-x) contains supplementary material, which is available to authorized users.

Highlights

Long-term neuroimmune activation is a common finding in major depressive disorder (MDD)
Body weight partly normalized 3 days after LPS injection. This is in line with previous experiments that showed that body weight is decreased up to 3 days after LPS injection [27]
phosphate-buffered saline (PBS) injection did not result in significant alterations in body weight

Summary

Introduction

Long-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain. Literature suggests that antidepressant van Buel et al Journal of Neuroinflammation (2015) 12:232 treatment may, at least in part, normalize neuroimmune changes associated with MDD [19,20,21]

Objectives

Methods

Results

Discussion

Conclusion