Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice

• Main Authors: Lim, Lee Wei, Shrestha, Smeeta, Or, Yu Zuan, Tan, Shawn Zheng Kai, Chung, Hwa Hwa, Sun, Yang, Lim, Chew Leng, Khairuddin, Sharafuddin, Lufkin, Thomas, Lin, Valerie Chun Ling
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2018
• Subjects: DRNTU::Science::Biological sciences; Tetratricopeptide Repeat Protein 9A; Anxiety Disorders
• Online Access: https://hdl.handle.net/10356/87632; http://hdl.handle.net/10220/46753
• Institution: Nanyang Technological University

Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A−/−) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A−/− mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A−/− mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A+/+ mice. This difference was abolished after ovariectomy, and administration of 17-β-estradiol benzoate (EB) restored this escalated anxiety-like behavior in TTC9A−/− mice. Since serotonin is well-known to be the key neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and serotonin transporter (5-HTT) were measured in the ventromedial prefrontal cortex (vmPFC) and dorsal raphe nucleus (DRN). Interestingly, the heightened anxiety in TTC9A−/− mice under EB influence is consistent with a greater induction of TPH 2, and 5-HTT by EB in DRN that play key roles in emotion regulation. In conclusion, our data indicate that TTC9A modulates the anxiety-related behaviors through modulation of estrogen action on the serotonergic system in the DRN.