Antigen‐Induced Arthritis in Mice induces Depression‐Like Behavior and Microglial Activation in Hippocampus after the Resolution of Peripheral Inflammation
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».