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Lack of seipin in neurons results in anxiety- and depression-like behaviors via down regulation of PPAR gamma
Zhou, Libin1,2; Yin, Jun2; Wang, Conghui2; Liao, Jiawei3,4; Liu, George3,4; Chen, Ling1,2
刊名HUMAN MOLECULAR GENETICS
2014-08-01
DOI10.1093/hmg/ddu126
23期:15页:4094-4102
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Genetics & Heredity
资助者NSFC ; NSFC
研究领域[WOS]Biochemistry & Molecular Biology ; Genetics & Heredity
关键词[WOS]CONGENITAL GENERALIZED LIPODYSTROPHY ; ACTIVATED-RECEPTOR-GAMMA ; FORCED SWIMMING TEST ; NEURAL STEM-CELLS ; HIPPOCAMPAL NEUROGENESIS ; ADIPOCYTE DIFFERENTIATION ; LIPID DROPLETS ; ADULT MALE ; MICE ; PROTEIN
英文摘要

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 (PPAR gamma) 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 17 beta-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 PPAR gamma levels. The PPAR gamma 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 PPAR gamma expression. Collectively, these results indicate that neuronal seipin deficiency causing reduced PPAR gamma levels leads to affective disorders in male mice that are rescued by E2-increased PPAR gamma expression.

语种英语
所属项目编号81361120247 ; 31171440 ; 81121061 ; 2014CB943303 ; 2011CB503900
资助者NSFC ; NSFC
WOS记录号WOS:000339669200016
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52430
专题基础医学院_心血管所
作者单位1.Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China
2.Nanjing Med Univ, Dept Physiol, Nanjing 210029, Jiangsu, Peoples R China
3.Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
4.Peking Univ, Key Lab Cardiovasc Sci, Beijing 100191, Peoples R China
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GB/T 7714
Zhou, Libin,Yin, Jun,Wang, Conghui,et al. Lack of seipin in neurons results in anxiety- and depression-like behaviors via down regulation of PPAR gamma[J]. HUMAN MOLECULAR GENETICS,2014,23(15):4094-4102.
APA Zhou, Libin,Yin, Jun,Wang, Conghui,Liao, Jiawei,Liu, George,&Chen, Ling.(2014).Lack of seipin in neurons results in anxiety- and depression-like behaviors via down regulation of PPAR gamma.HUMAN MOLECULAR GENETICS,23(15),4094-4102.
MLA Zhou, Libin,et al."Lack of seipin in neurons results in anxiety- and depression-like behaviors via down regulation of PPAR gamma".HUMAN MOLECULAR GENETICS 23.15(2014):4094-4102.
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