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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.
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Research Article Inflammation Neuroscience

Electroconvulsive stimulation attenuates chronic neuroinflammation

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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

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Figure 2

ECS inhibits chronic neuroinflammation.

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ECS inhibits chronic neuroinflammation.
Pathological analysis was obtain...
Pathological analysis was obtained at the end of the experiment at day 95 p.i. from ECS-treated versus sham-treated (control) mice as shown on Figure 1C. In all graphs, the horizontal lines (and gray zone) represent the median value (± minima/maxima) of naive, age-matched Biozzi mice. (A–E) Immunofluorescence staining for CD3 in control EAE (A and B) and ECS-treated EAE (C and D) showed that ECS induced a 59% reduction in the total amount of CD3+ T cells in spinal cord white matter CD3+ cell quantification is provided as total number of cells per (uniformly cut) section (E). The white squares in A and C are enlarged in B and D, respectively; arrowheads point to CD3+ cells. (F–H) Immunofluorescence staining for IBA1 in control EAE (F) and ECS-treated EAE (G) showed that ECS induced a 44% reduction in IBA1+ cells in spinal cord white matter (SC WM) (H). IBA1+ cell quantification is provided as number of cells per microscopic field. (I–K) Immunofluorescence staining for GFAP in control EAE (I) and ECS-treated EAE (J) showed that ECS induced a 35% reduction in GFAP+ cells in SC WM (H). GFAP+ cell quantification is provided as number of cells per microscopic field. P values calculated with Student’s unpaired t test. Box-and-whisker plots show quartiles with median, and with minima and maxima at the bottom and top whiskers, respectively.

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