Antigen‐Induced Arthritis in Mice induces Depression‐Like Behavior and Microglial Activation in Hippocampus after the Resolution of Peripheral Inflammation
Bibliographic record
Abstract
Rheumatic Arthritis (RA) affects 1 in 100 adults globally and is of unknown etiology. RA is characterized by inflammation that affects most commonly the joints and relapsing symptoms, such as swollen, painful and tender joints, and joint stiffness. RA is also accompanied by neurological and psychological manifestations including chronic pain, fatigue, depression, social withdrawal and weight loss that together significantly reduce quality‐of‐life in those affected by RA. While efforts to understand the mechanisms of joint inflammation have led to important treatments, such as anti‐TNFα therapy, the mechanisms that lead to the chronic pain and depression observed in patients with RA, even in remission, have yet to be uncovered. The aim of this work was to develop a model that reproduces in rodents the depression‐like phenotype observed in patients with RA and assess the mechanisms underlying these changes. Antigen‐induced arthritis (AIA) was induced in 8–10 weeks old C57BL/6J mice by sensitization with methylated bovine serum albumin (mBSA) followed by intra‐articular challenge 14 days later. Depression‐like behavior was assessed using the tail suspension test (TST). Immunohistochemistry was used to investigate microglial activation (based on Iba1 immunoreactivity), and multiplex assay to measure cytokine levels in different regions of the brain. As reported previously, the peak of inflammatory response in the knee of mice with AIA was observed 24 h after challenge and inflammation was no longer observed at 13 days as gauged by the number of infiltrated neutrophils to the knee cavity. However, 13 days after the challenge, AIA mice displayed depression‐like behaviors; spending a longer immobility time in the TST compared with controls; this behavioral effect was reversed by the antidepressant imipramine. Depression‐like behaviors were not observed at the peak of joint inflammation. Iba1 expression was increased in the hippocampus of mice with AIA at 13 days, suggesting microglial activation in this region after the resolution of peripheral inflammation. Iba1 immunoreactivity in the circumventricular organs of mice 13d after AIA challenge was not different to tissue from control mice. Multiplex assay revealed an increase in KC, MCP‐1 and TNFa in the hippocampus in mice with AIA at the peak of the inflammation that was not maintained 13 days after challenge, suggesting that the maintenance of microglial activation is not dependent on local cytokine production. In conclusion, this is the first report of an animal model of arthritis that reproduces depression‐like behavior after the resolution of peripheral inflammation. This is associated with microglial activation in the hippocampus. Support or Funding Information Canadian Institutes of Health Research This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".