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Elevated reactive aggression in forebrain-specific Ccn2 knockout mice
Ho-Ching Chang1, Chi-Hou Ng1, Yu-Fu Chen2
1College of Medicine Graduate Institute of Anatomy and Cell Biology National Taiwan University Taipei Taiwan.
Abstract:
Cellular communication network factor 2 (CCN2) is a matricellular protein that plays important roles in connective tissue. CCN2 is also expressed in the nervous system; however, its role is still unclear. To explore CCN2 function in the brain, we generated forebrain-specific Ccn2 knockout (FbCcn2 KO) mice. In this study, we examined the behavioral phenotypes of FbCcn2KO mice. Male mice lacking CCN2 in the forebrain exhibited normal locomotion, sensorimotor gating, and social behaviors but signs of anxiety and elevated reactive aggression. We checked the c-fos expression in aggression-related brain regions following the resident-intruder task (RIT), an aggression test. RIT-induced c-fos levels in the medial amygdala (MeA) were higher in FbCcn2 -/- mice as compared to controls. However, in the prefrontal cortex, RIT-induced c-fos levels in FbCcn2 -/- mice were lower than controls. Our results suggested in male mice lacking CCN2 in the olfaction-related regions, olfactory social cues elicit greater signals in the MeA, resulting in greater reactive aggression in the RIT. Further, lacking CCN2 in the prefrontal cortex, the major area related to inhibitory control and emotion regulation, may lead to signs of anxiety and the failure to suppress aggressive behaviors. Our model is useful in elaborating the mechanism underlying reactive aggression and therapeutic strategies.
Insights
Forebrain-specific knockout of cellular communication network factor 2 (CCN2) in male mice resulted in increased anxiety and reactive aggression. This suggests CCN2
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Genetics
Background:
- Cellular communication network factor 2 (CCN2) is a matricellular protein with known roles in connective tissue.
- CCN2 is expressed in the nervous system, but its specific functions in the brain remain largely uncharacterized.
- Understanding CCN2's role in the brain is crucial for elucidating neural communication and behavior.
Purpose of the Study:
- To investigate the function of CCN2 in the brain by examining the behavioral phenotypes of forebrain-specific Ccn2 knockout (FbCcn2 KO) mice.
- To explore the neural mechanisms underlying aggression and anxiety related to CCN2 deficiency in the forebrain.
- To establish a mouse model for studying reactive aggression and potential therapeutic strategies.
Main Methods:
- Generation of forebrain-specific Ccn2 knockout (FbCcn2 KO) mice.
- Assessment of behavioral phenotypes including locomotion, sensorimotor gating, social behavior, anxiety, and reactive aggression.
- Analysis of c-fos expression in aggression-related brain regions (medial amygdala and prefrontal cortex) following the resident-intruder task (RIT).
Main Results:
- Male FbCcn2 KO mice displayed normal locomotion, sensorimotor gating, and social behaviors.
- FbCcn2 KO mice exhibited increased signs of anxiety and elevated reactive aggression.
- RIT-induced c-fos expression was higher in the medial amygdala but lower in the prefrontal cortex of FbCcn2 KO mice compared to controls.
Conclusions:
- Loss of CCN2 in the forebrain, particularly in olfaction-related regions, enhances olfactory social cue signaling in the medial amygdala, leading to increased reactive aggression.
- Reduced CCN2 in the prefrontal cortex may impair inhibitory control and emotion regulation, contributing to anxiety and aggressive behavior.
- The FbCcn2 KO mouse model provides insights into the mechanisms of reactive aggression and potential therapeutic interventions.
