Elevated reactive aggression in forebrain‐specific Ccn2 knockout mice

• Published in: Journal of cell communication and signaling Vol. 18; no. 3; pp. e12040 - n/a
• Main Authors: Chang, Ho‐Ching, Ng, Chi‐Hou, Chen, Yu‐Fu, Wang, Yu‐Chun, Yu, I‐Shing, Lee, Lukas Jyuhn‐Hsiarn, Lee, Li‐Jen, Lee, Kuang‐Yung
• Format: Journal Article
• Language: English
• Published: Hoboken John Wiley and Sons Inc 01-09-2024
• Subjects: c‐fos; medial amygdala; olfactory system; prefrontal cortex; resident‐intruder test
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1002/ccs3.12040

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.
Cellular communication network factor 2 (CCN2) is expressed in the olfactory bulb, anterior olfactory nucleus, frontal cortex (FC), and cortical layer IVb. Intruder mice elicit greater neuronal signals in the medial amygdala, in mice lacking CCN2, resulting in greater reactive aggression during resident‐intruder task. Further, lacking CCN2 in the FC, may lead to the failure of suppressing aggressive behaviors.