title: Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Lee Wei
authors.initials: LW
authors.lastname: Lim
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Smeeta
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Yu Zuan
authors.initials: YZ
authors.lastname: Or
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Shawn Zheng Kai
authors.initials: SZ
authors.lastname: Tan
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Hwa Hwa
authors.initials: HH
authors.lastname: Chung
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Chew Leng
authors.initials: CL
authors.lastname: Lim
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
authors.forename: Sharafuddin
authors.initials: S
authors.lastname: Khairuddin
authors.affiliation: Department of Biology, Clarkson University, Potsdam, New York, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lufkin
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Valerie Chun Ling
authors.initials: VC
authors.lastname: Lin
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal; D065847:Dorsal Raphe Nucleus / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism*; D010641:Phenotype; D010684:Philosophy; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D004967:Estrogens; D008840:Microfilament Proteins; D012333:RNA, Messenger; C577874:tetratricopeptide repeat protein 9A, mouse; D012701:Serotonin; D014365:Tryptophan Hydroxylase