Connective tissue growth factor (CTGF) is a novel pro-depressant molecule
Turner CA, Sharma V, Hagenauer MH, Aydin C, O'Connor AM, Thompson RC, Watson SJ, Akil H
Society for Neuroscience. 2017.
Little is known about the role of connective tissue growth factor (CTGF) in the brain. We evaluated the expression of CTGF in our selectively bred model of response to a novel environment, where bLRs exhibit increased anxiety-like and depression-like behavior compared to bHRs. We also assessed the expression of CTGF in the human amygdala of individuals with Major Depressive Disorder (MDD). To understand its role in affective behavior, we administered CTGF to rodents acutely and chronically and tested their affective responses. We then assessed the ability of an anti-CTGF antibody (FG-3019) to alter emotionality and gene expression. Finally, we assessed CTGF expression in various stress paradigms. In three nuclei of the human amygdala, CTGF expression was increased in individuals with MDD compared to controls. In the bHR/bLR model, CTGF expression was significantly increased in the dentate gyrus (DG) of bLRs in adulthood compared to bHRs. When the highly anxious LRs were administered early life fibroblast growth factor-2 (FGF2), a treatment known to decrease anxiety later in life, the expression of CTGF decreased in the DG in adulthood. In outbred animals, acute CTGF (400ng, i.c.v.) increased depression-like behavior. Moreover, both acute and chronic treatment with FG-3019 was antidepressant. Chronic treatment with FG-3019 also altered the expression of molecules that interact with CTGF, as well as decreasing CTGF itself. Finally, four days of social defeat stress in LRs significantly increased CTGF expression in the dentate gyrus. However, two weeks of chronic variable stress in bLRs decreased CTGF expression in the hippocampus. Thus, the region, nature and/or temporal dynamics of the stress are important. In conclusion, molecules that inhibit or decrease CTGF expression may be effective antidepressants.