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: Libin Zhou, Jun Yin, Conghui Wang, Jiawei Liao, George Liu, Ling Chen
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 23 Issue 15 Pg. 4094-102 (Aug 01 2014) ISSN: 1460-2083 [Electronic] England
• PMID: 24651066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Bscl2 protein, mouse
• GTP-Binding Protein gamma Subunits
• PPAR gamma
• Thiazolidinediones
• Rosiglitazone
• Testosterone
• Estradiol
• Heterotrimeric GTP-Binding Proteins

Topics

• Animals
• Anxiety (drug therapy, genetics, metabolism, physiopathology)
• Behavior, Animal (drug effects)
• Cerebral Cortex (drug effects, metabolism, physiopathology)
• Depression (drug therapy, genetics, metabolism, physiopathology)
• Estradiol (blood, pharmacology)
• Female
• GTP-Binding Protein gamma Subunits
• Gene Expression Regulation
• Heterotrimeric GTP-Binding Proteins (deficiency, genetics)
• Hindlimb Suspension
• Hippocampus (drug effects, metabolism, physiopathology)
• Male
• Maze Learning (drug effects)
• Mice
• Mice, Knockout
• Neurons (drug effects, metabolism, pathology)
• PPAR gamma (agonists, genetics, metabolism)
• Rosiglitazone
• Rotarod Performance Test
• Sex Factors
• Swimming
• Testosterone (blood)
• Thiazolidinediones (pharmacology)