Complement C3 and C3aR mediate different aspects of emotional behaviours; relevance to risk for psychiatric disorder
| Autor: | Sophie A. Brain, Jack Reddaway, Trevor Humby, Timothy R. Hughes, Margarita Toneva, William P. Gray, Andreea-Ingrid Baloc, Jeremy Hall, B. Paul Morgan, Lawrence Stephen Wilkinson, Anna L. Moon, Laura J. Westacott, Niels Haan, Michael J. Owen, Emma-Louise Bush |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
medicine.medical_specialty
Immunology Inflammation Mice 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Immune system Emotionality medicine Animals Psychiatry 030304 developmental biology 0303 health sciences biology Endocrine and Autonomic Systems Mental Disorders Complement C3 Receptors Complement Complement system Complement (complexity) Disease Models Animal biology.protein Anxiety iC3b C3a receptor medicine.symptom Psychology 030217 neurology & neurosurgery Signal Transduction |
| ISSN: | 0889-1591 |
| Popis: | Complement is a key component of the immune system with roles in inflammation and host-defence. Here we reveal novel functions of complement pathways impacting on emotional reactivity of potential relevance to the emerging links between complement and risk for psychiatric disorder. We used mouse models to assess the effects of manipulating components of the complement system on emotionality. Mice lacking the complement C3a Receptor (C3aR-/-) demonstrated a selective increase in unconditioned (innate) anxiety whilst mice deficient in the central complement component C3 (C3-/-) showed a selective increase in conditioned (learned) fear. The dissociable behavioural phenotypes were linked to different signalling mechanisms. Effects on innate anxiety were independent of C3a, the canonical ligand for C3aR, consistent with the existence of an alternative ligand mediating innate anxiety, whereas effects on learned fear were due to loss of iC3b/CR3 signalling. Our findings show that specific elements of the complement system and associated signalling pathways contribute differentially to heightened states of anxiety and fear commonly seen in psychopathology. |
| Databáze: | OpenAIRE |
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