RT Journal Article
SR Electronic
T1 Electroconvulsive shock enhances responsive motility and purinergic currents in microglia in the mouse hippocampus
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0056-19.2019
DO 10.1523/ENEURO.0056-19.2019
A1 Alberto Sepulveda-Rodriguez
A1 Pinggan Li
A1 Tahiyana Khan
A1 James D. Ma
A1 Colby A. Carlone
A1 P. Lorenzo Bozzelli
A1 Katherine E. Conant
A1 Patrick A. Forcelli
A1 Stefano Vicini
YR 2019
UL http://www.eneuro.org/content/early/2019/04/15/ENEURO.0056-19.2019.abstract
AB Microglia are in a privileged position to both affect and be affected by neuroinflammation, neuronal activity and injury, which are all hallmarks of seizures and the epilepsies. Hippocampal microglia become activated after prolonged, damaging seizures known as Status Epilepticus (SE). However, since SE causes both hyperactivity and injury of neurons, the mechanisms triggering this activation remain unclear, as does the relevance of the microglial activation to the ensuing epileptogenic processes. In this study, we use electroconvulsive shock (ECS) to study the effect of neuronal hyperactivity without neuronal degeneration on mouse hippocampal microglia. Unlike SE, ECS did not alter hippocampal CA1 microglial density, morphology or baseline motility. In contrast, both ECS and SE produced a similar increase in ATP-directed microglial process motility in acute slices, and similarly upregulated expression of the chemokine CCL2. Whole-cell patch-clamp recordings of hippocampal CA1sr microglia showed that ECS enhanced purinergic currents mediated by P2X7 receptors in the absence of changes in passive properties or voltage-gated currents, or changes in receptor expression. This differs from previously described alterations in intrinsic characteristics which coincided with enhanced purinergic currents following SE. These ECS-induced effects point to a “seizure signature” in hippocampal microglia characterized by altered purinergic signaling. These data demonstrate that ictal activity per se can drive alterations in microglial physiology without neuronal injury. These physiological changes, which up until now have been associated with prolonged and damaging seizures, are of added interest as they may be relevant to electroconvulsive therapy, which remains a gold-standard treatment for depression.SIGNIFICANCE STATEMENT Epilepsy is the 4th most prevalent neurological disease, affecting 1 in 26 people over their lifetime. There is a critical unmet need in understanding basic mechanisms underlying the development of epilepsy (epileptogenesis), given that no disease-modifying treatments are currently available. How specific features of microglial activation contribute to subsequent epileptogenesis, and how seizure activity, per se, triggers changes in microglial responses is understudied. In this study, we demonstrate that hippocampal microglia react acutely to single non-epileptogenic seizures, in ways reminiscent of SE-induced activation. Thus, key features of the microglial activation pattern observed after SE may not be related to the epileptogenic process, and further work is needed to fully characterize the interplay between microglia, seizures and epilepsy.