Archival ReportInflammatory T Helper 17 Cells Promote Depression-like Behavior in Mice
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Mice and Behavioral Assessments
C57BL/6 and C57BL/6-129 Rorc(γT)+/GFP (6–12 weeks) male mice were from the Jackson Laboratories (Bar Harbor, Maine) and GSK3S21A/S21A/S9A/S9A knockin mice were from Dr. Dario Alessi (University of Dundee, United Kingdom). Six-week-old mice were used to prepare T cells, while 8- to 12-week-old mice were used for behavioral assessments. The Rorc(γT)+/GFP mice were obtained by crossing Rorc(γT)+/GFP×Rorc(γT)+/GFP to produce 50% Rorc(γT)+/GFP, 25% wild-type, and 25% Rorc(γT)GFP/GFP mice and
Results
Stress is a critical factor in promoting susceptibility to depression 2, 38 and is modeled in rodents with the learned helplessness paradigm of depression-like behavior (39) to assess modulators of mood, while limitations of animal models are also well recognized 38, 40, 41. The traditional learned helplessness paradigm involves stressing mice with mild, unpredictable, and inescapable footshocks (IES) and typically 24 hours later exposing mice to mild footshocks from which they are free to
Discussion
The growing evidence of causative links between inflammation and depression 3, 4 indicates that targets of inflammatory molecules contribute to establishing a prodepressant environment. This study focused on T cells because they are major sensors of the cytokine environment, each subtype of T helper CD4+ cell responds to a different cytokine signature, and, importantly, T cells are more enduring than transiently expressed cytokines, potentially enabling T cells to contribute to the prolonged
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