title: Lack of seipin in neurons results in anxiety- and depression-like behaviors via down regulation of PPARγ.
abstract: The Seipin gene was originally found to be responsible for type 2 congenital lipodystrophy and involved in lipid droplet formation. Seipin is highly expressed in the central nervous system as well. Seipin mutations have been identified in motor neuron diseases such as Silver syndrome and spastic paraplegia. In this study, we generated neuron-specific seipin knockout mice (seipin-nKO) to investigate the influence of seipin deficiency on locomotion and affective behaviors. In comparison with control mice, 8-week-old male seipin-nKO mice, but not female mice, displayed anxiety- and depression-like behaviors as assessed by open-field, elevated plus-maze, forced swim and tail suspension tests. However, neither male nor female seipin-nKO mice showed locomotion deficits in swimming tank and rotarod tests. Interestingly, the mRNA and protein levels of peroxisome proliferator-activated receptor gamma (PPARγ) in the hippocampus and cortex were lower in male seipin-nKO mice, but not female mice, than controls. In seipin-nKO mice, plasma levels of sex hormones including 17β-estradiol (E2) in females and testosterone in males as well as corticosterone were not altered compared with controls. The treatment of male seipin-nKO mice with E2 ameliorated the anxiety- and depression-like behaviors and remarkably increased PPARγ levels. The PPARγ agonist rosiglitazone alleviated affective disorders in male seipin-nKO mice. Notably, anxiety- and depression-like behaviors appeared in female seipin-nKO mice after ovariectomy, which was associated with low PPARγ expression. Collectively, these results indicate that neuronal seipin deficiency causing reduced PPARγ levels leads to affective disorders in male mice that are rescued by E2-increased PPARγ expression.
authors.affiliation: State Key Laboratory of Reproductive Medicine and Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Conghui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, China Administration of Education, Beijing 100191, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Liao
authors.affiliation: Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, China Administration of Education, Beijing 100191, China lingchen@njmu.edu.cn georgeliu@bjmu.edu.cn.
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine and Department of Physiology, Nanjing Medical University, Nanjing 210029, China lingchen@njmu.edu.cn georgeliu@bjmu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D005260:Female; D044388:GTP-Binding Protein gamma Subunits; D005786:Gene Expression Regulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D000077154:Rosiglitazone; D045442:Rotarod Performance Test; D012737:Sex Factors; D013550:Swimming; D013739:Testosterone / Q000097:blood; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C115783:Bscl2 protein, mouse; D044388:GTP-Binding Protein gamma Subunits; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013739:Testosterone; D004958:Estradiol; D020962:Heterotrimeric GTP-Binding Proteins