136. Increased Expression of Early Complement Components in Frontal Cortex in Schizophrenia
Notice bibliographique
Résumé
Background: The complement system is a key effector of innate immunity, mediating elimination of pathogens and debris via initiation of phagocytosis, inflammation, and cell lysis. Intriguingly, recent studies have identified an additional role for early complement components, including C1q, C3, and C4, in synaptic pruning and remodeling. Mounting evidence suggests that dysregulation of the complement system occurs in schizophrenia. Increased activation and concentration of complement components has been reported in blood, while complement C4 was recently identified as a major genetic risk factor. However, little is known about expression of complement components in brain tissue in this disorder. The aim of this study was therefore to compare protein and mRNA expression of early complement components in frontal cortex in schizophrenia and control subjects. Methods: Protein and/or mRNA expression of the early complement components C1q, C3 and C4, and the regulator C1-inhibitor, was quantified in 35 individuals with SCZ and 35 controls. Samples were obtained from the orbital–frontal and dorsolateral prefrontal regions courtesy of the Stanley Medical Research Institute. Proteins were quantified in dorsolateral prefrontal cortex by immunoblotting, and mRNA expression measured in orbital–frontal cortex using quantitative PCR. Measures were compared between groups using analysis of variance. Results: C1-inhibitor was higher in the schizophrenia group. While C4 mRNA expression was increased in schizophrenia, C4 protein levels did not differ between groups, despite the presence of a positive correlation between protein and mRNA expression. Of note, C4 genotype was associated with C4 protein levels. Furthermore, C4 protein levels were negatively correlated with levels of the synaptic protein SNAP-25. Finally, positive correlations were observed between early complement components and markers of peripheral and/or central inflammation. Conclusion: Overall, our results are consistent with a dysregulation of the complement system in schizophrenia. Increased complement expression may be indicative of an inflammatory response. However, early complement components have also been implicated in synaptic pruning and circuit remodeling. Observed correlations between complement C4 and SNAP-25 suggest the complement system may play a role in triggering the synaptic disturbances previously identified in schizophrenia. Funding: This work was supported by the Canadian Institutes of Health Research.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
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 ».