Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Electroconvulsive stimulation attenuates chronic neuroinflammation
Smadar Goldfarb, … , Nina Fainstein, Tamir Ben-Hur
Smadar Goldfarb, … , Nina Fainstein, Tamir Ben-Hur
Published August 11, 2020
Citation Information: JCI Insight. 2020;5(17):e137028. https://doi.org/10.1172/jci.insight.137028.
View: Text | PDF
Research Article Inflammation Neuroscience

Electroconvulsive stimulation attenuates chronic neuroinflammation

  • Text
  • PDF
Abstract

Electroconvulsive therapy is highly effective in resistant depression by unknown mechanisms. Microglial toxicity was suggested to mediate depression and plays key roles in neuroinflammatory and degenerative diseases, where there is critical shortage in therapies. We examined the effects of electroconvulsive seizures (ECS) on chronic neuroinflammation and microglial neurotoxicity. Electric brain stimulation inducing full tonic-clonic seizures during chronic relapsing–progressive experimental autoimmune encephalomyelitis (EAE) reduced spinal immune cell infiltration, reduced myelin and axonal loss, and prevented clinical deterioration. Using the transfer EAE model, we examined the effect of ECS on systemic immune response in donor mice versus ECS effect on CNS innate immune activity in recipient mice. ECS did not affect encephalitogenicity of systemic T cells, but it targeted the CNS directly to inhibit T cell–induced neuroinflammation. In vivo and ex vivo assays indicated that ECS suppressed microglial neurotoxicity by reducing inducible NOS expression, nitric oxide, and reactive oxygen species (ROS) production, and by reducing CNS oxidative stress. Microglia from ECS-treated EAE mice expressed less T cell stimulatory and chemoattractant factors. Our findings indicate that electroconvulsive therapy targets the CNS innate immune system to reduce neuroinflammation by attenuating microglial neurotoxicity. These findings signify a potentially novel therapeutic approach for chronic neuroinflammatory, neuropsychiatric, and neurodegenerative diseases.

Authors

Smadar Goldfarb, Nina Fainstein, Tamir Ben-Hur

×

Figure 7

ECS reduces oxidative injury in spinal cords of ECS-treated EAE mice.

Options: View larger image (or click on image) Download as PowerPoint
ECS reduces oxidative injury in spinal cords of ECS-treated EAE mice.
(A...
(A and B) Immunofluorescence staining for MDA in SC sections of EAE Biozzi mice (day 95 p.i.). ECS reduced the number of oxidative injured MDA+ cells (shown as fraction of total cells) within the white matter (WM) and gray matter (GM) of the SC (C). In A and B, the dashed lines demarcate the WM/GM border, arrows point at MDA+ cells in the WM, and chevron arrows point at MDA+ cells in the GM. (D) Double staining for NeuN (marker for neurons) and MDA showing localization of MDA staining in neurons in the GM of EAE mice, marked by arrowheads. (E) Double staining for APC (marker for oligodendrocytes) and MDA showing localization of MDA staining in oligodendrocytes in the WM of EAE mice, marked by arrowheads. Box-and-whisker plot shows quartiles with median, and with minima and maxima at the bottom and top whiskers, respectively. P values calculated with Student’s unpaired t test.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts